Skip to main content
Top
Published in: Fluids and Barriers of the CNS 1/2021

Open Access 01-12-2021 | Obesity | Review

SARS-CoV-2: is there neuroinvasion?

Authors: Conor McQuaid, Molly Brady, Rashid Deane

Published in: Fluids and Barriers of the CNS | Issue 1/2021

Login to get access

Abstract

Background

SARS-CoV-2, a coronavirus (CoV), is known to cause acute respiratory distress syndrome, and a number of non-respiratory complications, particularly in older male patients with prior health conditions, such as obesity, diabetes and hypertension. These prior health conditions are associated with vascular dysfunction, and the CoV disease 2019 (COVID-19) complications include multiorgan failure and neurological problems. While the main route of entry into the body is inhalation, this virus has been found in many tissues, including the choroid plexus and meningeal vessels, and in neurons and CSF.

Main body

We reviewed SARS-CoV-2/COVID-19, ACE2 distribution and beneficial effects, the CNS vascular barriers, possible mechanisms by which the virus enters the brain, outlined prior health conditions (obesity, hypertension and diabetes), neurological COVID-19 manifestation and the aging cerebrovascualture. The overall aim is to provide the general reader with a breadth of information on this type of virus and the wide distribution of its main receptor so as to better understand the significance of neurological complications, uniqueness of the brain, and the pre-existing medical conditions that affect brain. The main issue is that there is no sound evidence for large flux of SARS-CoV-2 into brain, at present, compared to its invasion of the inhalation pathways.

Conclusions

While SARS-CoV-2 is detected in brains from severely infected patients, it is unclear on how it gets there. There is no sound evidence of SARS-CoV-2 flux into brain to significantly contribute to the overall outcomes once the respiratory system is invaded by the virus. The consensus, based on the normal route of infection and presence of SARS-CoV-2 in severely infected patients, is that the olfactory mucosa is a possible route into brain. Studies are needed to demonstrate flux of SARS-CoV-2 into brain, and its replication in the parenchyma to demonstrate neuroinvasion. It is possible that the neurological manifestations of COVID-19 are a consequence of mainly cardio-respiratory distress and multiorgan failure. Understanding potential SARS-CoV-2 neuroinvasion pathways could help to better define the non-respiratory neurological manifestation of COVID-19.
Literature
2.
go back to reference Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288:192–206.PubMedCrossRef Pascarella G, Strumia A, Piliego C, Bruno F, Del Buono R, Costa F, et al. COVID-19 diagnosis and management: a comprehensive review. J Intern Med. 2020;288:192–206.PubMedCrossRef
3.
go back to reference Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993–8.PubMedPubMedCentralCrossRef Tenforde MW, Kim SS, Lindsell CJ, Billig Rose E, Shapiro NI, Files DC, et al. Symptom duration and risk factors for delayed return to usual health among outpatients with COVID-19 in a multistate health care systems network—United States, March–June 2020. MMWR Morb Mortal Wkly Rep. 2020;69(30):993–8.PubMedPubMedCentralCrossRef
6.
go back to reference Miyazato Y, Morioka S, Tsuzuki S, Akashi M, Osanai Y, Tanaka K, et al. Prolonged and late-onset symptoms of coronavirus disease 2019. Open Forum Infect Dis. 2020;7(11):ofaa507.PubMedPubMedCentralCrossRef Miyazato Y, Morioka S, Tsuzuki S, Akashi M, Osanai Y, Tanaka K, et al. Prolonged and late-onset symptoms of coronavirus disease 2019. Open Forum Infect Dis. 2020;7(11):ofaa507.PubMedPubMedCentralCrossRef
9.
go back to reference Dalan R, Bornstein SR, El-Armouche A, Rodionov RN, Markov A, Wielockx B, et al. The ACE-2 in COVID-19: foe or friend? Horm Metab Res. 2020;52(05):257–63.PubMedPubMedCentralCrossRef Dalan R, Bornstein SR, El-Armouche A, Rodionov RN, Markov A, Wielockx B, et al. The ACE-2 in COVID-19: foe or friend? Horm Metab Res. 2020;52(05):257–63.PubMedPubMedCentralCrossRef
11.
go back to reference Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457–60.PubMedPubMedCentralCrossRef Xu X, Chen P, Wang J, Feng J, Zhou H, Li X, et al. Evolution of the novel coronavirus from the ongoing Wuhan outbreak and modeling of its spike protein for risk of human transmission. Sci China Life Sci. 2020;63(3):457–60.PubMedPubMedCentralCrossRef
12.
go back to reference Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci NLM (Medline). 2020;16:1753–66.CrossRef Yi Y, Lagniton PNP, Ye S, Li E, Xu RH. COVID-19: what has been learned and to be learned about the novel coronavirus disease. Int J Biol Sci NLM (Medline). 2020;16:1753–66.CrossRef
13.
go back to reference Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459–68.PubMedPubMedCentralCrossRef Gordon DE, Jang GM, Bouhaddou M, Xu J, Obernier K, White KM, et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature. 2020;583:459–68.PubMedPubMedCentralCrossRef
14.
go back to reference ‘Li Y, Zhou W, Yang L, You R. Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor. Pharmacol Res 2020;157(January):19–20. ‘Li Y, Zhou W, Yang L, You R. Physiological and pathological regulation of ACE2, the SARS-CoV-2 receptor. Pharmacol Res 2020;157(January):19–20.
17.
go back to reference Ramphul K, Mejias SG. Kawasaki disease: a comprehensive review. Arch Med Sci Atheroscler Dis. 2018;3(1):41–5.CrossRef Ramphul K, Mejias SG. Kawasaki disease: a comprehensive review. Arch Med Sci Atheroscler Dis. 2018;3(1):41–5.CrossRef
19.
go back to reference Ya M. Properties of coronavirus and SARS-CoV-2. Malays J Pathol. 2020;42(1):3–11. Ya M. Properties of coronavirus and SARS-CoV-2. Malays J Pathol. 2020;42(1):3–11.
20.
go back to reference Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou J-J, et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature. 2020;583:286–9.PubMedCrossRef Xiao K, Zhai J, Feng Y, Zhou N, Zhang X, Zou J-J, et al. Isolation of SARS-CoV-2-related coronavirus from Malayan pangolins. Nature. 2020;583:286–9.PubMedCrossRef
21.
go back to reference Das G, Mukherjee N, Ghosh S. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020;11(9):1206–9.PubMedCrossRef Das G, Mukherjee N, Ghosh S. Neurological Insights of COVID-19 Pandemic. ACS Chem Neurosci. 2020;11(9):1206–9.PubMedCrossRef
22.
go back to reference Ortega JT, Serrano ML, Pujol FH, Rangel HR. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: an in silico analysis. EXCLI J. 2020;19:410–7.PubMedPubMedCentral Ortega JT, Serrano ML, Pujol FH, Rangel HR. Role of changes in SARS-CoV-2 spike protein in the interaction with the human ACE2 receptor: an in silico analysis. EXCLI J. 2020;19:410–7.PubMedPubMedCentral
23.
24.
go back to reference Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. 2020 Mar 14;2020.03.14.988345. Wang K, Chen W, Zhou Y-S, Lian J-Q, Zhang Z, Du P, et al. SARS-CoV-2 invades host cells via a novel route: CD147-spike protein. bioRxiv. 2020 Mar 14;2020.03.14.988345.
25.
go back to reference Avolio E, Gamez M, Kapil Gupta ;, Foster R, Berger I, Caputo M, et al. The SARS-CoV-2 spike protein disrupts the cooperative function of human cardiac pericytes—endothelial cells through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. https://doi.org/10.1101/2020.12.21.423721 Avolio E, Gamez M, Kapil Gupta ;, Foster R, Berger I, Caputo M, et al. The SARS-CoV-2 spike protein disrupts the cooperative function of human cardiac pericytes—endothelial cells through CD147 receptor-mediated signalling: a potential non-infective mechanism of COVID-19 microvascular disease. https://​doi.​org/​10.​1101/​2020.​12.​21.​423721
26.
go back to reference Alejandra Tortorici M, Walls AC, Lang Y, Wang C, Li Z, Koerhuis D, et al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol. 2019;26(6):481–9.PubMedPubMedCentralCrossRef Alejandra Tortorici M, Walls AC, Lang Y, Wang C, Li Z, Koerhuis D, et al. Structural basis for human coronavirus attachment to sialic acid receptors. Nat Struct Mol Biol. 2019;26(6):481–9.PubMedPubMedCentralCrossRef
28.
go back to reference Rathnasinghe R, Jangra S, Cupic A, Martínez-Romero C, Mulder LCF, Kehrer T, et al. The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera Contributed equally. medRxiv. 2021;2021.01.19.21249592. Rathnasinghe R, Jangra S, Cupic A, Martínez-Romero C, Mulder LCF, Kehrer T, et al. The N501Y mutation in SARS-CoV-2 spike leads to morbidity in obese and aged mice and is neutralized by convalescent and post-vaccination human sera Contributed equally. medRxiv. 2021;2021.01.19.21249592.
29.
go back to reference Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, et al. Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell. 2021;184(1):64-75.e11.PubMedPubMedCentralCrossRef Volz E, Hill V, McCrone JT, Price A, Jorgensen D, O’Toole Á, et al. Evaluating the effects of SARS-CoV-2 spike mutation D614G on transmissibility and pathogenicity. Cell. 2021;184(1):64-75.e11.PubMedPubMedCentralCrossRef
30.
go back to reference Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182(4):812-827.e19.PubMedPubMedCentralCrossRef Korber B, Fischer WM, Gnanakaran S, Yoon H, Theiler J, Abfalterer W, et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Cell. 2020;182(4):812-827.e19.PubMedPubMedCentralCrossRef
31.
go back to reference Yang X, Chen X, Bian G, Tu J, Xing Y, Wang Y, et al. Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease. J Gen Virol. 2014;95(PART3):614–26.PubMedCrossRef Yang X, Chen X, Bian G, Tu J, Xing Y, Wang Y, et al. Proteolytic processing, deubiquitinase and interferon antagonist activities of Middle East respiratory syndrome coronavirus papain-like protease. J Gen Virol. 2014;95(PART3):614–26.PubMedCrossRef
32.
33.
go back to reference Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH, et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2021;370(6523):1464–8.CrossRef Hou YJ, Chiba S, Halfmann P, Ehre C, Kuroda M, Dinnon KH, et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. Science. 2021;370(6523):1464–8.CrossRef
36.
go back to reference Greaney AJ, Loes AN, Crawford KH, Starr TN, Malone KD, Chu HY, et al. Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies. bioRxiv. 2021 Jan 4;2020.12.31.425021. Greaney AJ, Loes AN, Crawford KH, Starr TN, Malone KD, Chu HY, et al. Comprehensive mapping of mutations to the SARS-CoV-2 receptor-binding domain that affect recognition by polyclonal human serum antibodies. bioRxiv. 2021 Jan 4;2020.12.31.425021.
37.
go back to reference Avanzato VA, Matson MJ, Seifert SN, Pryce R, Williamson BN, Anzick SL, et al. Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell. 2020;183(7):1901-1912.e9.PubMedPubMedCentralCrossRef Avanzato VA, Matson MJ, Seifert SN, Pryce R, Williamson BN, Anzick SL, et al. Case study: prolonged infectious SARS-CoV-2 shedding from an asymptomatic immunocompromised individual with cancer. Cell. 2020;183(7):1901-1912.e9.PubMedPubMedCentralCrossRef
38.
go back to reference Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2—what do they mean? JAMA. 2021;325:529–31.PubMedCrossRef Lauring AS, Hodcroft EB. Genetic variants of SARS-CoV-2—what do they mean? JAMA. 2021;325:529–31.PubMedCrossRef
39.
go back to reference WHO | SARS-CoV-2 mink-associated variant strain—Denmark. WHO. 2020. WHO | SARS-CoV-2 mink-associated variant strain—Denmark. WHO. 2020.
40.
go back to reference Maison DP, Ching LL, Shikuma CM, Nerurkar VR. Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation. bioRxiv. 2021 Jan 7;2021.01.06.425497. Maison DP, Ching LL, Shikuma CM, Nerurkar VR. Genetic Characteristics and Phylogeny of 969-bp S Gene Sequence of SARS-CoV-2 from Hawaii Reveals the Worldwide Emerging P681H Mutation. bioRxiv. 2021 Jan 7;2021.01.06.425497.
41.
go back to reference Wang R, Chen J, Gao K, Hozumi Y, Yin C, Wei G-W. Analysis of SARS-CoV-2 mutations in the United States suggests presence of four substrains and novel variants. Commun Biol. 2021;4(1):228.PubMedPubMedCentralCrossRef Wang R, Chen J, Gao K, Hozumi Y, Yin C, Wei G-W. Analysis of SARS-CoV-2 mutations in the United States suggests presence of four substrains and novel variants. Commun Biol. 2021;4(1):228.PubMedPubMedCentralCrossRef
42.
go back to reference Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci Transl Med 2011;3(84):84ra44–84ra44. Yu YJ, Zhang Y, Kenrick M, Hoyte K, Luk W, Lu Y, et al. Boosting brain uptake of a therapeutic antibody by reducing its affinity for a transcytosis target. Sci Transl Med 2011;3(84):84ra44–84ra44.
43.
go back to reference Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, et al. Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA. 2020;323:2089–90.PubMedPubMedCentralCrossRef Spinato G, Fabbris C, Polesel J, Cazzador D, Borsetto D, Hopkins C, et al. Alterations in smell or taste in mildly symptomatic outpatients with SARS-CoV-2 infection. JAMA. 2020;323:2089–90.PubMedPubMedCentralCrossRef
45.
go back to reference Mallard C. Innate immune regulation by toll-like receptors in the brain. International Scholarly Research Network ISRN Neurology. 2012. Mallard C. Innate immune regulation by toll-like receptors in the brain. International Scholarly Research Network ISRN Neurology. 2012.
48.
go back to reference See H, Wark P. Innate immune response to viral infection of the lungs. Paediatr Respir Rev. 2008;8:243–50.CrossRef See H, Wark P. Innate immune response to viral infection of the lungs. Paediatr Respir Rev. 2008;8:243–50.CrossRef
49.
go back to reference Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20(6):669–77.PubMedPubMedCentralCrossRef Verity R, Okell LC, Dorigatti I, Winskill P, Whittaker C, Imai N, et al. Estimates of the severity of coronavirus disease 2019: a model-based analysis. Lancet Infect Dis. 2020;20(6):669–77.PubMedPubMedCentralCrossRef
51.
52.
go back to reference Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE, Mack M, et al. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Investig. 2019;129(9):3625–39.PubMedPubMedCentralCrossRef Channappanavar R, Fehr AR, Zheng J, Wohlford-Lenane C, Abrahante JE, Mack M, et al. IFN-I response timing relative to virus replication determines MERS coronavirus infection outcomes. J Clin Investig. 2019;129(9):3625–39.PubMedPubMedCentralCrossRef
53.
go back to reference Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30.PubMedCrossRef Salama C, Han J, Yau L, Reiss WG, Kramer B, Neidhart JD, et al. Tocilizumab in patients hospitalized with covid-19 pneumonia. N Engl J Med. 2021;384(1):20–30.PubMedCrossRef
54.
go back to reference Engelhardt B, Ransohoff RM. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 2005;26:485–95.PubMedCrossRef Engelhardt B, Ransohoff RM. The ins and outs of T-lymphocyte trafficking to the CNS: anatomical sites and molecular mechanisms. Trends Immunol. 2005;26:485–95.PubMedCrossRef
56.
go back to reference Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020;55(5). Zhang C, Wu Z, Li JW, Zhao H, Wang GQ. The cytokine release syndrome (CRS) of severe COVID-19 and Interleukin-6 receptor (IL-6R) antagonist Tocilizumab may be the key to reduce the mortality. Int J Antimicrob Agents. 2020;55(5).
57.
go back to reference Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemostasis 2020. Connors JM, Levy JH. Thromboinflammation and the hypercoagulability of COVID-19. J Thromb Haemostasis 2020.
58.
go back to reference Rodríguez A, Tjärnlund A, Ivanji J, Singh M, García I, Williams A, et al. Role of IgA in the defense against respiratory infections: IgA deficient mice exhibited increased susceptibility to intranasal infection with Mycobacterium bovis BCG. Vaccine. 2005;23(20):2565–72.PubMedCrossRef Rodríguez A, Tjärnlund A, Ivanji J, Singh M, García I, Williams A, et al. Role of IgA in the defense against respiratory infections: IgA deficient mice exhibited increased susceptibility to intranasal infection with Mycobacterium bovis BCG. Vaccine. 2005;23(20):2565–72.PubMedCrossRef
62.
go back to reference Chen HD, Fraire AE, Joris I, Welsh RM, Selin LK. Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. American Journal of Pathology [Internet]. 2003 Oct 1. 163(4):1341–55. https://pubmed.ncbi.nlm.nih.gov/14507643/. Accessed 6 June 2021. Chen HD, Fraire AE, Joris I, Welsh RM, Selin LK. Specific history of heterologous virus infections determines anti-viral immunity and immunopathology in the lung. American Journal of Pathology [Internet]. 2003 Oct 1. 163(4):1341–55. https://​pubmed.​ncbi.​nlm.​nih.​gov/​14507643/​. Accessed 6 June 2021.
63.
go back to reference Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;28:1–12. Tay MZ, Poh CM, Rénia L, MacAry PA, Ng LFP. The trinity of COVID-19: immunity, inflammation and intervention. Nat Rev Immunol. 2020;28:1–12.
64.
go back to reference Yilla M, Harcourt BH, Hickman CJ, McGrew M, Tamin A, Goldsmith CS, et al. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005;107(1):93–101.PubMedCrossRef Yilla M, Harcourt BH, Hickman CJ, McGrew M, Tamin A, Goldsmith CS, et al. SARS-coronavirus replication in human peripheral monocytes/macrophages. Virus Res. 2005;107(1):93–101.PubMedCrossRef
65.
go back to reference Campillo-Navarro M, Chávez-Blanco AD, Wong-Baeza I, Serafín-López J, Flores-Mejía R, Estrada-Parra S, et al. Mast cells in lung homeostasis: Beyond type i hypersensitivity. Corp Commun. 2005;10(2):115–23. Campillo-Navarro M, Chávez-Blanco AD, Wong-Baeza I, Serafín-López J, Flores-Mejía R, Estrada-Parra S, et al. Mast cells in lung homeostasis: Beyond type i hypersensitivity. Corp Commun. 2005;10(2):115–23.
66.
go back to reference Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The role of apelin in cardiovascular diseases, obesity and cancer. Vol. 9, Frontiers in Physiology. Frontiers Media S.A.; 2018. Wysocka MB, Pietraszek-Gremplewicz K, Nowak D. The role of apelin in cardiovascular diseases, obesity and cancer. Vol. 9, Frontiers in Physiology. Frontiers Media S.A.; 2018.
68.
go back to reference Kuba K, Imai Y, Penninger JM. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J. 2013;77:301–8.PubMedCrossRef Kuba K, Imai Y, Penninger JM. Multiple functions of angiotensin-converting enzyme 2 and its relevance in cardiovascular diseases. Circ J. 2013;77:301–8.PubMedCrossRef
69.
go back to reference Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T, et al. Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci USA. 2008;105(22):7809–14.PubMedPubMedCentralCrossRef Haga S, Yamamoto N, Nakai-Murakami C, Osawa Y, Tokunaga K, Sata T, et al. Modulation of TNF-α-converting enzyme by the spike protein of SARS-CoV and ACE2 induces TNF-α production and facilitates viral entry. Proc Natl Acad Sci USA. 2008;105(22):7809–14.PubMedPubMedCentralCrossRef
70.
go back to reference Swärd P, Edsfeldt A, Reepalu A, Jehpsson L, Rosengren BE, Karlsson MK. Age and sex differences in soluble ACE2 may give insights for COVID-19. Crit Care. 2020;24:221.PubMedPubMedCentralCrossRef Swärd P, Edsfeldt A, Reepalu A, Jehpsson L, Rosengren BE, Karlsson MK. Age and sex differences in soluble ACE2 may give insights for COVID-19. Crit Care. 2020;24:221.PubMedPubMedCentralCrossRef
71.
go back to reference Beneteau-Burnat B, Baudin B, Morgant G, Baumann FC, Giboudeau J. Serum angiotensin-converting enzyme in healthy and sarcoidotic children: Comparison with the reference interval for adults. Clin Chem. 1990;36(2):344–6.PubMedCrossRef Beneteau-Burnat B, Baudin B, Morgant G, Baumann FC, Giboudeau J. Serum angiotensin-converting enzyme in healthy and sarcoidotic children: Comparison with the reference interval for adults. Clin Chem. 1990;36(2):344–6.PubMedCrossRef
72.
go back to reference Li W, Moore MJ, Vasllieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–4.PubMedPubMedCentralCrossRef Li W, Moore MJ, Vasllieva N, Sui J, Wong SK, Berne MA, et al. Angiotensin-converting enzyme 2 is a functional receptor for the SARS coronavirus. Nature. 2003;426(6965):450–4.PubMedPubMedCentralCrossRef
73.
go back to reference Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, et al. Tumor necrosis factor-α convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J Biol Chem. 2005;280(34):30113–9.PubMedCrossRef Lambert DW, Yarski M, Warner FJ, Thornhill P, Parkin ET, Smith AI, et al. Tumor necrosis factor-α convertase (ADAM17) mediates regulated ectodomain shedding of the severe-acute respiratory syndrome-coronavirus (SARS-CoV) receptor, angiotensin-converting enzyme-2 (ACE2). J Biol Chem. 2005;280(34):30113–9.PubMedCrossRef
74.
go back to reference Patel VB, Clarke N, Wang Z, Fan D, Parajuli N, Basu R, et al. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J Mol Cell Cardiol. 2014;1(66):167–76.CrossRef Patel VB, Clarke N, Wang Z, Fan D, Parajuli N, Basu R, et al. Angiotensin II induced proteolytic cleavage of myocardial ACE2 is mediated by TACE/ADAM-17: a positive feedback mechanism in the RAS. J Mol Cell Cardiol. 2014;1(66):167–76.CrossRef
75.
go back to reference Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215–20.PubMedCrossRef Lan J, Ge J, Yu J, Shan S, Zhou H, Fan S, et al. Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor. Nature. 2020;581(7807):215–20.PubMedCrossRef
76.
go back to reference Sun P, Lu X, Xu C, Wang Y, Sun W, Xi J. CD-sACE2 inclusion compounds: an effective treatment for coronavirus disease 2019 (COVID-19). J Med Virol. 2020;92:1721–3.PubMedCrossRef Sun P, Lu X, Xu C, Wang Y, Sun W, Xi J. CD-sACE2 inclusion compounds: an effective treatment for coronavirus disease 2019 (COVID-19). J Med Virol. 2020;92:1721–3.PubMedCrossRef
77.
go back to reference Swärd P, Edsfeldt A, Reepalu A, Jehpsson L, Rosengren BE, Karlsson MK. Age and sex differences in soluble ACE2 may give insights for COVID-19. Crit Care. 2020;24:1–3.CrossRef Swärd P, Edsfeldt A, Reepalu A, Jehpsson L, Rosengren BE, Karlsson MK. Age and sex differences in soluble ACE2 may give insights for COVID-19. Crit Care. 2020;24:1–3.CrossRef
78.
go back to reference Hoffmann M, Kleine-Weber H, Schroeder S, Mü MA, Drosten C, Pö S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.PubMedPubMedCentralCrossRef Hoffmann M, Kleine-Weber H, Schroeder S, Mü MA, Drosten C, Pö S. SARS-CoV-2 cell entry depends on ACE2 and TMPRSS2 and is blocked by a clinically proven protease inhibitor. Cell. 2020;181:271–80.PubMedPubMedCentralCrossRef
79.
go back to reference McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, McAllen RM, et al. The brain renin-angiotensin system: Location and physiological roles. Int J Biochem Cell Biol. 2003;35:901–18.PubMedCrossRef McKinley MJ, Albiston AL, Allen AM, Mathai ML, May CN, McAllen RM, et al. The brain renin-angiotensin system: Location and physiological roles. Int J Biochem Cell Biol. 2003;35:901–18.PubMedCrossRef
80.
go back to reference Carey RM. The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 2015;22:204–10.PubMedCrossRef Carey RM. The intrarenal renin-angiotensin system in hypertension. Adv Chronic Kidney Dis. 2015;22:204–10.PubMedCrossRef
81.
go back to reference Alenina N, Bader M. ACE2 in brain physiology and pathophysiology: evidence from transgenic animal models. Neurochem Res. 2019;44(6):1323–9.PubMedCrossRef Alenina N, Bader M. ACE2 in brain physiology and pathophysiology: evidence from transgenic animal models. Neurochem Res. 2019;44(6):1323–9.PubMedCrossRef
82.
go back to reference Zhang Q, Cong M, Wang N, Li X, Zhang H, Zhang K, et al. Association of angiotensin-converting enzyme 2 gene polymorphism and enzymatic activity with essential hypertension in different gender a case–control study. Medicine. 2018;97(42):e12917.PubMedPubMedCentralCrossRef Zhang Q, Cong M, Wang N, Li X, Zhang H, Zhang K, et al. Association of angiotensin-converting enzyme 2 gene polymorphism and enzymatic activity with essential hypertension in different gender a case–control study. Medicine. 2018;97(42):e12917.PubMedPubMedCentralCrossRef
83.
go back to reference Evans CE, Miners JS, Piva G, Willis CL, Heard DM, Kidd EJ, et al. ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease. Acta Neuropathol. 2020;139(3):485–502.PubMedPubMedCentralCrossRef Evans CE, Miners JS, Piva G, Willis CL, Heard DM, Kidd EJ, et al. ACE2 activation protects against cognitive decline and reduces amyloid pathology in the Tg2576 mouse model of Alzheimer’s disease. Acta Neuropathol. 2020;139(3):485–502.PubMedPubMedCentralCrossRef
84.
go back to reference Li L-J, Zhang F-B, Liu S-Y, Tian Y-H, Le F, Wang L-Y, et al. Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization. Biol Reprod. 2014;90(6):125.PubMedCrossRef Li L-J, Zhang F-B, Liu S-Y, Tian Y-H, Le F, Wang L-Y, et al. Human sperm devoid of germinal angiotensin-converting enzyme is responsible for total fertilization failure and lower fertilization rates by conventional in vitro fertilization. Biol Reprod. 2014;90(6):125.PubMedCrossRef
85.
go back to reference Hemnes AR, Rathinasabapathy A, Austin EA, Brittain EL, Carrier EJ, Chen X, et al. A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension. Eur Respir J. 2018;51(6):1702638.PubMedPubMedCentralCrossRef Hemnes AR, Rathinasabapathy A, Austin EA, Brittain EL, Carrier EJ, Chen X, et al. A potential therapeutic role for angiotensin-converting enzyme 2 in human pulmonary arterial hypertension. Eur Respir J. 2018;51(6):1702638.PubMedPubMedCentralCrossRef
88.
go back to reference Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112–6.PubMedPubMedCentralCrossRef Imai Y, Kuba K, Rao S, Huan Y, Guo F, Guan B, et al. Angiotensin-converting enzyme 2 protects from severe acute lung failure. Nature. 2005;436(7047):112–6.PubMedPubMedCentralCrossRef
89.
go back to reference Da Silva JS, Gabriel-Costa D, Wang H, Ahmad S, Sun X, Varagic J, et al. Blunting of cardioprotective actions of estrogen in female rodent heart linked to altered expression of cardiac tissue chymase and ACE2. J Renin-Angiotensin-Aldosterone Syst 2017. Doi: https://doi.org/10.1177/1470320317722270 Da Silva JS, Gabriel-Costa D, Wang H, Ahmad S, Sun X, Varagic J, et al. Blunting of cardioprotective actions of estrogen in female rodent heart linked to altered expression of cardiac tissue chymase and ACE2. J Renin-Angiotensin-Aldosterone Syst 2017. Doi: https://​doi.​org/​10.​1177/​1470320317722270​
90.
go back to reference Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7.PubMedPubMedCentralCrossRef Hamming I, Timens W, Bulthuis MLC, Lely AT, Navis GJ, van Goor H. Tissue distribution of ACE2 protein, the functional receptor for SARS coronavirus. A first step in understanding SARS pathogenesis. J Pathol. 2004;203(2):631–7.PubMedPubMedCentralCrossRef
91.
go back to reference Xu D, Ma M, Xu Y, Su Y, Ong S-B, Hu X, et al. Single-cell transcriptome analysis indicates new potential regulation mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2 2 3. Xu D, Ma M, Xu Y, Su Y, Ong S-B, Hu X, et al. Single-cell transcriptome analysis indicates new potential regulation mechanism of ACE2 and NPs signaling among heart failure patients infected with SARS-CoV-2 2 3.
92.
go back to reference Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):1–5.CrossRef Xu H, Zhong L, Deng J, Peng J, Dan H, Zeng X, et al. High expression of ACE2 receptor of 2019-nCoV on the epithelial cells of oral mucosa. Int J Oral Sci. 2020;12(1):1–5.CrossRef
93.
go back to reference Sakima A, Averill DB, Gallagher PE, Kasper SO, Tommasi EN, Ferrario CM, et al. Impaired heart rate baroreflex in older rats: role of endogenous angiotensin-(1–7) at the nucleus tractus solitarii. Hypertension. 2005;46(2):333–40.PubMedCrossRef Sakima A, Averill DB, Gallagher PE, Kasper SO, Tommasi EN, Ferrario CM, et al. Impaired heart rate baroreflex in older rats: role of endogenous angiotensin-(1–7) at the nucleus tractus solitarii. Hypertension. 2005;46(2):333–40.PubMedCrossRef
94.
go back to reference Elased KM, Cunha TS, Gurley SB, Coffman TM, Morris M. New mass spectrometric assay for angiotensin-converting enzyme 2 activity. Hypertension. 2006;47(5):1010–7.PubMedCrossRef Elased KM, Cunha TS, Gurley SB, Coffman TM, Morris M. New mass spectrometric assay for angiotensin-converting enzyme 2 activity. Hypertension. 2006;47(5):1010–7.PubMedCrossRef
97.
go back to reference Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R373–81.PubMedCrossRef Doobay MF, Talman LS, Obr TD, Tian X, Davisson RL, Lazartigues E. Differential expression of neuronal ACE2 in transgenic mice with overexpression of the brain renin-angiotensin system. Am J Physiol Regul Integr Comp Physiol. 2007;292(1):R373–81.PubMedCrossRef
98.
go back to reference Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood–brain barrier. Neurobiol Dis. 2020;146:105131.PubMedPubMedCentralCrossRef Buzhdygan TP, DeOre BJ, Baldwin-Leclair A, Bullock TA, McGary HM, Khan JA, et al. The SARS-CoV-2 spike protein alters barrier function in 2D static and 3D microfluidic in-vitro models of the human blood–brain barrier. Neurobiol Dis. 2020;146:105131.PubMedPubMedCentralCrossRef
99.
go back to reference Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020 Jun 22;2020.06.22.20137273. Horby P, Lim WS, Emberson J, Mafham M, Bell J, Linsell L, et al. Effect of dexamethasone in hospitalized patients with COVID-19: preliminary report. medRxiv. 2020 Jun 22;2020.06.22.20137273.
100.
go back to reference Ghobrial M, Charish J, Takada S, Valiante T, Monnier PP, Radovanovic I, et al. The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors. bioRxiv. 2020. Ghobrial M, Charish J, Takada S, Valiante T, Monnier PP, Radovanovic I, et al. The human brain vasculature shows a distinct expression pattern of SARS-CoV-2 entry factors. bioRxiv. 2020.
101.
go back to reference He L, Mäe MA, Sun Y, Muhl L, Nahar K, Liébanas EV, et al. Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2—implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients. bioRxiv. 2020 May 12;2020.05.11.088500. He L, Mäe MA, Sun Y, Muhl L, Nahar K, Liébanas EV, et al. Pericyte-specific vascular expression of SARS-CoV-2 receptor ACE2—implications for microvascular inflammation and hypercoagulopathy in COVID-19 patients. bioRxiv. 2020 May 12;2020.05.11.088500.
102.
go back to reference Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.PubMedPubMedCentralCrossRef Ou X, Liu Y, Lei X, Li P, Mi D, Ren L, et al. Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV. Nat Commun. 2020;11(1):1620.PubMedPubMedCentralCrossRef
103.
go back to reference Li Y, Bai W, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552–5.PubMedCrossRef Li Y, Bai W, Hashikawa T. The neuroinvasive potential of SARS-CoV2 may play a role in the respiratory failure of COVID-19 patients. J Med Virol. 2020;92(6):552–5.PubMedCrossRef
104.
go back to reference Li Y, Zhang Z, Yang L, Xin S, Cao P, Lu J. The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. 2020; Li Y, Zhang Z, Yang L, Xin S, Cao P, Lu J. The MERS-CoV receptor DPP4 as a candidate binding target of the SARS-CoV-2 spike. 2020;
105.
go back to reference Zlokovic BV. The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders. Neuron. 2008;57:178–201.PubMedCrossRef Zlokovic BV. The Blood-Brain Barrier in Health and Chronic Neurodegenerative Disorders. Neuron. 2008;57:178–201.PubMedCrossRef
106.
go back to reference Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6(JUL):1–22. Wong AD, Ye M, Levy AF, Rothstein JD, Bergles DE, Searson PC. The blood-brain barrier: an engineering perspective. Front Neuroeng. 2013;6(JUL):1–22.
107.
go back to reference Zlokovic BV. Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci. 2005;28(4):202–8.PubMedCrossRef Zlokovic BV. Neurovascular mechanisms of Alzheimer’s neurodegeneration. Trends Neurosci. 2005;28(4):202–8.PubMedCrossRef
108.
go back to reference Schlageter KE, Molnar P, Lapin GD, Groothuis DR. Microvessel organization and structure in experimental brain tumors: Microvessel populations with distinctive structural and functional properties. Microvasc Res. 1999;58(3):312–28.PubMedCrossRef Schlageter KE, Molnar P, Lapin GD, Groothuis DR. Microvessel organization and structure in experimental brain tumors: Microvessel populations with distinctive structural and functional properties. Microvasc Res. 1999;58(3):312–28.PubMedCrossRef
109.
go back to reference Rhea EM, Salameh TS, Logsdon AF, Hanson AJ, Erickson MA, Banks WA. Blood-Brain Barriers in Obesity. AAPS Journal. 2017;19(4):921–30.CrossRef Rhea EM, Salameh TS, Logsdon AF, Hanson AJ, Erickson MA, Banks WA. Blood-Brain Barriers in Obesity. AAPS Journal. 2017;19(4):921–30.CrossRef
111.
go back to reference Deane R, Zheng W, Zlokovic BV. Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem. 2004;88(4):813–20.PubMedPubMedCentralCrossRef Deane R, Zheng W, Zlokovic BV. Brain capillary endothelium and choroid plexus epithelium regulate transport of transferrin-bound and free iron into the rat brain. J Neurochem. 2004;88(4):813–20.PubMedPubMedCentralCrossRef
112.
go back to reference Mw B. The structure and function of the blood-brain barrier. Fed Proc. 1984;43(2):186–90. Mw B. The structure and function of the blood-brain barrier. Fed Proc. 1984;43(2):186–90.
113.
go back to reference Zheng W, Deane R, Redzic Z, Preston JE, Segal MB. Transport of L-[125I]thyroxine by in situ perfused ovine choroid plexus: inhibition by lead exposure. J Toxicol Environ Health Part A. 2003;66(5):435–51.CrossRef Zheng W, Deane R, Redzic Z, Preston JE, Segal MB. Transport of L-[125I]thyroxine by in situ perfused ovine choroid plexus: inhibition by lead exposure. J Toxicol Environ Health Part A. 2003;66(5):435–51.CrossRef
114.
go back to reference Deane R, LaRue B, Sagare AP, Castellino FJ, Zhong Z, Zlokovic BV. Endothelial protein C receptor-assisted transport of activated protein C across the mouse blood-brain barrier. J Cerebral Blood Flow Metabol. 2009;29(1):25–33.CrossRef Deane R, LaRue B, Sagare AP, Castellino FJ, Zhong Z, Zlokovic BV. Endothelial protein C receptor-assisted transport of activated protein C across the mouse blood-brain barrier. J Cerebral Blood Flow Metabol. 2009;29(1):25–33.CrossRef
116.
117.
go back to reference Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.PubMedCrossRef Abbott NJ, Patabendige AAK, Dolman DEM, Yusof SR, Begley DJ. Structure and function of the blood-brain barrier. Neurobiol Dis. 2010;37(1):13–25.PubMedCrossRef
118.
go back to reference Jiménez AJ, Domínguez-Pinos MD, Guerra MM, Fernández-Llebrez P, Pérez-Fígares JM. Structure and function of the ependymal barrier and diseases associated with ependyma disruption. Tissue Barriers. 2014;2:1–14.CrossRef Jiménez AJ, Domínguez-Pinos MD, Guerra MM, Fernández-Llebrez P, Pérez-Fígares JM. Structure and function of the ependymal barrier and diseases associated with ependyma disruption. Tissue Barriers. 2014;2:1–14.CrossRef
120.
go back to reference Bouillé C, Mesnil M, Barriere H, Gabrion J. Gap junctional intercellular communication between cultured ependymal cells, revealed by lucifer yellow CH transfer and freeze-fracture. Glia. 1991;4(1):25–36.PubMedCrossRef Bouillé C, Mesnil M, Barriere H, Gabrion J. Gap junctional intercellular communication between cultured ependymal cells, revealed by lucifer yellow CH transfer and freeze-fracture. Glia. 1991;4(1):25–36.PubMedCrossRef
122.
go back to reference Söhl G, Odermatt B, Maxeiner S, Degen J, Willecke K. New insights into the expression and function of neural connexins with transgenic mouse mutants. In: Brain Research Reviews. Brain Res Brain Res Rev; 2004. p. 245–59. Söhl G, Odermatt B, Maxeiner S, Degen J, Willecke K. New insights into the expression and function of neural connexins with transgenic mouse mutants. In: Brain Research Reviews. Brain Res Brain Res Rev; 2004. p. 245–59.
123.
go back to reference Yamamoto T, Kardami E, Nagy JI. Basic fibroblast growth factor in rat brain: localization to glial gap junctions correlates with connexin43 distribution. Brain Res. 1991;554(1–2):336–43.PubMedCrossRef Yamamoto T, Kardami E, Nagy JI. Basic fibroblast growth factor in rat brain: localization to glial gap junctions correlates with connexin43 distribution. Brain Res. 1991;554(1–2):336–43.PubMedCrossRef
124.
go back to reference Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J, et al. Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development. 2005;132(23):5329–39.PubMedCrossRef Banizs B, Pike MM, Millican CL, Ferguson WB, Komlosi P, Sheetz J, et al. Dysfunctional cilia lead to altered ependyma and choroid plexus function, and result in the formation of hydrocephalus. Development. 2005;132(23):5329–39.PubMedCrossRef
126.
go back to reference Liddelow SA. Development of the choroid plexus and blood-CSF barrier. Vol. 9, Frontiers in Neuroscience. Frontiers Media S.A.; 2015. Liddelow SA. Development of the choroid plexus and blood-CSF barrier. Vol. 9, Frontiers in Neuroscience. Frontiers Media S.A.; 2015.
127.
go back to reference Davson H, Segal MB. Effect of cerebrospinal fluid on volume of distribution of extracellular markers. Vol. 92, Brain. 1969. Davson H, Segal MB. Effect of cerebrospinal fluid on volume of distribution of extracellular markers. Vol. 92, Brain. 1969.
128.
go back to reference Davson H, Segal MB. The effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid and the brain. J Physiol. 1970;209(1):131–53.PubMedPubMedCentralCrossRef Davson H, Segal MB. The effects of some inhibitors and accelerators of sodium transport on the turnover of 22Na in the cerebrospinal fluid and the brain. J Physiol. 1970;209(1):131–53.PubMedPubMedCentralCrossRef
129.
go back to reference Davson H, Hollingsworth G, Segal MB. The mechanism of drainage of the cerebrospinal fluid. Vol. 93, Brain. 1970. Davson H, Hollingsworth G, Segal MB. The mechanism of drainage of the cerebrospinal fluid. Vol. 93, Brain. 1970.
130.
go back to reference Davson H, Segal MB, Malcolm B. Physiology of the CSF and blood-brain barriers. CRC Press; 1996, p. 822. Davson H, Segal MB, Malcolm B. Physiology of the CSF and blood-brain barriers. CRC Press; 1996, p. 822.
131.
go back to reference Johanson CE, Duncan JA, Klinge PM, Brinker T, Stopa EG, Silverberg GD. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res. 2008;5:32.CrossRef Johanson CE, Duncan JA, Klinge PM, Brinker T, Stopa EG, Silverberg GD. Multiplicity of cerebrospinal fluid functions: new challenges in health and disease. Cerebrospinal Fluid Res. 2008;5:32.CrossRef
132.
go back to reference Pollay M. The function and structure of the cerebrospinal fluid outflow system. Cerebrospinal Fluid Res. 2010;7:20.CrossRef Pollay M. The function and structure of the cerebrospinal fluid outflow system. Cerebrospinal Fluid Res. 2010;7:20.CrossRef
134.
go back to reference Fame RM, Lehtinen MK. Emergence and developmental roles of the cerebrospinal fluid system. Developmental Cell. Cell Press; 2020. p. 261–75. Fame RM, Lehtinen MK. Emergence and developmental roles of the cerebrospinal fluid system. Developmental Cell. Cell Press; 2020. p. 261–75.
135.
go back to reference Bradbury MW, Westrop RJ. Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J Physiol. 1983;339(1):519–34.PubMedPubMedCentralCrossRef Bradbury MW, Westrop RJ. Factors influencing exit of substances from cerebrospinal fluid into deep cervical lymph of the rabbit. J Physiol. 1983;339(1):519–34.PubMedPubMedCentralCrossRef
136.
go back to reference Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 2004;1(1):1–3.CrossRef Johnston M, Zakharov A, Papaiconomou C, Salmasi G, Armstrong D. Evidence of connections between cerebrospinal fluid and nasal lymphatic vessels in humans, non-human primates and other mammalian species. Cerebrospinal Fluid Res. 2004;1(1):1–3.CrossRef
137.
go back to reference Kida S, Pantazis A, Weller RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol. 1993;19(6):480–8.PubMedCrossRef Kida S, Pantazis A, Weller RO. CSF drains directly from the subarachnoid space into nasal lymphatics in the rat. Anatomy, histology and immunological significance. Neuropathol Appl Neurobiol. 1993;19(6):480–8.PubMedCrossRef
138.
go back to reference Brady M, Rahman A, Combs A, Venkatraman C, Kasper RT, McQuaid C, et al. Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging. Fluids Barriers CNS. 2020;17(1):71.PubMedPubMedCentralCrossRef Brady M, Rahman A, Combs A, Venkatraman C, Kasper RT, McQuaid C, et al. Cerebrospinal fluid drainage kinetics across the cribriform plate are reduced with aging. Fluids Barriers CNS. 2020;17(1):71.PubMedPubMedCentralCrossRef
139.
go back to reference Davson H, Welch K, Segal MB. The physiology and pathophysiology of the cerebrospinal fluid. Ann Neurol. 1987;24(1):106–106. Davson H, Welch K, Segal MB. The physiology and pathophysiology of the cerebrospinal fluid. Ann Neurol. 1987;24(1):106–106.
142.
go back to reference Falangola MF, Hanly A, Galvao-Castro B, Petito CK. HIV infection of human choroid plexus: a possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol. 1995;54(4):497–503.PubMedCrossRef Falangola MF, Hanly A, Galvao-Castro B, Petito CK. HIV infection of human choroid plexus: a possible mechanism of viral entry into the CNS. J Neuropathol Exp Neurol. 1995;54(4):497–503.PubMedCrossRef
143.
go back to reference Bragg DC, Childers TA, Tompkins MB, Tompkins WA, Meeker RB. Infection of the choroid plexus by feline immunodeeciency virus. J Neurovirol. 2002;8:211–24.PubMedCrossRef Bragg DC, Childers TA, Tompkins MB, Tompkins WA, Meeker RB. Infection of the choroid plexus by feline immunodeeciency virus. J Neurovirol. 2002;8:211–24.PubMedCrossRef
145.
go back to reference Finsterer, Josef Stollberger C. Update on the neurology of COVID-19. 2020;0–3. Finsterer, Josef Stollberger C. Update on the neurology of COVID-19. 2020;0–3.
146.
go back to reference Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;1(94):55–8.CrossRef Moriguchi T, Harii N, Goto J, Harada D, Sugawara H, Takamino J, et al. A first case of meningitis/encephalitis associated with SARS-Coronavirus-2. Int J Infect Dis. 2020;1(94):55–8.CrossRef
147.
go back to reference Huang YH, Jiang D, Huang JT. SARS-CoV-2 detected in cerebrospinal fluid by PCR in a case of COVID-19 encephalitis. Brain Behav Immunity. 2020;87:149.CrossRef Huang YH, Jiang D, Huang JT. SARS-CoV-2 detected in cerebrospinal fluid by PCR in a case of COVID-19 encephalitis. Brain Behav Immunity. 2020;87:149.CrossRef
148.
go back to reference Garg R. Spectrum of neurological manifestations in covid-19: a review. Neurol India. 2020;68(3):560.PubMedCrossRef Garg R. Spectrum of neurological manifestations in covid-19: a review. Neurol India. 2020;68(3):560.PubMedCrossRef
149.
go back to reference Engelhardt B, Vajkoczy P, Weller RO. The movers and shapers in immune privilege of the CNS. Berlin: Nature Publishing Group; 2017.CrossRef Engelhardt B, Vajkoczy P, Weller RO. The movers and shapers in immune privilege of the CNS. Berlin: Nature Publishing Group; 2017.CrossRef
150.
go back to reference Bajénoff M, Germain RN. Seeing is believing: a focus on the contribution of microscopic imaging to our understanding of immune system function. Eur J Immunol. 2007;37(SUPPL. 1):S18-33.PubMedCrossRef Bajénoff M, Germain RN. Seeing is believing: a focus on the contribution of microscopic imaging to our understanding of immune system function. Eur J Immunol. 2007;37(SUPPL. 1):S18-33.PubMedCrossRef
151.
go back to reference Bousso P, Bhakta NR, Lewis RS, Robey E. Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science. 2002;296(5574):1876–80.PubMedCrossRef Bousso P, Bhakta NR, Lewis RS, Robey E. Dynamics of thymocyte-stromal cell interactions visualized by two-photon microscopy. Science. 2002;296(5574):1876–80.PubMedCrossRef
153.
go back to reference Hoeve MA, Nash AA, Jackson D, Randall RE, Dransfield I. Influenza virus A infection of human monocyte and macrophage subpopulations reveals increased susceptibility associated with cell differentiation. PLoS ONE. 2012;7(1):29443.CrossRef Hoeve MA, Nash AA, Jackson D, Randall RE, Dransfield I. Influenza virus A infection of human monocyte and macrophage subpopulations reveals increased susceptibility associated with cell differentiation. PLoS ONE. 2012;7(1):29443.CrossRef
157.
go back to reference Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv. 2020; Mao L, Wang M, Chen S, He Q, Chang J, Hong C, et al. Neurological Manifestations of Hospitalized Patients with COVID-19 in Wuhan, China: a retrospective case series study. medRxiv. 2020;
158.
go back to reference Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279–84.PubMedPubMedCentralCrossRef Li Y, Li M, Wang M, Zhou Y, Chang J, Xian Y, et al. Acute cerebrovascular disease following COVID-19: a single center, retrospective, observational study. Stroke Vasc Neurol. 2020;5(3):279–84.PubMedPubMedCentralCrossRef
159.
go back to reference Zach H, Dirkx MF, Pasman JW, Bloem BR, Helmich RC. Cognitive stress reduces the effect of levodopa on Parkinson’s resting tremor. CNS Neurosci Ther. 2017;23(3):209–15.PubMedPubMedCentralCrossRef Zach H, Dirkx MF, Pasman JW, Bloem BR, Helmich RC. Cognitive stress reduces the effect of levodopa on Parkinson’s resting tremor. CNS Neurosci Ther. 2017;23(3):209–15.PubMedPubMedCentralCrossRef
160.
go back to reference Ehgoetz Martens KA, Hall JM, Georgiades MJ, Gilat M, Walton CC, Matar E, et al. The functional network signature of heterogeneity in freezing of gait. Brain. 2018;141(4):1145–60.PubMedCrossRef Ehgoetz Martens KA, Hall JM, Georgiades MJ, Gilat M, Walton CC, Matar E, et al. The functional network signature of heterogeneity in freezing of gait. Brain. 2018;141(4):1145–60.PubMedCrossRef
161.
go back to reference Macht M, Kaussner Y, Möller JC, Stiasny-Kolster K, Eggert KM, Krüger HP, et al. Predictors of freezing in Parkinson’s disease: a survey of 6,620 patients. Mov Disord. 2007;22(7):953–6.PubMedCrossRef Macht M, Kaussner Y, Möller JC, Stiasny-Kolster K, Eggert KM, Krüger HP, et al. Predictors of freezing in Parkinson’s disease: a survey of 6,620 patients. Mov Disord. 2007;22(7):953–6.PubMedCrossRef
162.
go back to reference Zach H, Dirkx M, Pasman JW, Bloem BR, Helmich RC. The patient’s perspective: the effect of levodopa on Parkinson symptoms. Parkinsonism Relat Disord. 2017;1(35):48–54.CrossRef Zach H, Dirkx M, Pasman JW, Bloem BR, Helmich RC. The patient’s perspective: the effect of levodopa on Parkinson symptoms. Parkinsonism Relat Disord. 2017;1(35):48–54.CrossRef
163.
go back to reference Castelnuovo G, Zhu X, Francisco R, Pedro M, Delvecchio E, Pedro Espada J, et al. Psychological symptoms and behavioral changes in children and adolescents during the early phase of COVID-19 quarantine in three European Countries. Frontiers in Psychiatry | www.frontiersin.org [Internet]. 2020;11:570164. www.frontiersin.org Castelnuovo G, Zhu X, Francisco R, Pedro M, Delvecchio E, Pedro Espada J, et al. Psychological symptoms and behavioral changes in children and adolescents during the early phase of COVID-19 quarantine in three European Countries. Frontiers in Psychiatry | www.​frontiersin.​org [Internet]. 2020;11:570164. www.​frontiersin.​org
164.
go back to reference Knell G, Robertson MC, Dooley EE, Burford K, Mendez KS. Health behavior changes during covid-19 pandemic and subsequent “stay-at-home” orders. Int J Environ Res Public Health. 2020;17(17):1–16.CrossRef Knell G, Robertson MC, Dooley EE, Burford K, Mendez KS. Health behavior changes during covid-19 pandemic and subsequent “stay-at-home” orders. Int J Environ Res Public Health. 2020;17(17):1–16.CrossRef
166.
go back to reference Morfopoulou S, Brown JR, Davies EG, Anderson G, Virasami A, Qasim W, et al. Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med. 2016;375(5):497–8.PubMedCrossRef Morfopoulou S, Brown JR, Davies EG, Anderson G, Virasami A, Qasim W, et al. Human coronavirus OC43 associated with fatal encephalitis. N Engl J Med. 2016;375(5):497–8.PubMedCrossRef
167.
go back to reference Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004;113(1 Pt 1):e73–6.PubMed Yeh EA, Collins A, Cohen ME, Duffner PK, Faden H. Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 2004;113(1 Pt 1):e73–6.PubMed
168.
go back to reference Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol. 2020;77(11):1366–72.CrossRef Merkler AE, Parikh NS, Mir S, Gupta A, Kamel H, Lin E, et al. Risk of ischemic stroke in patients with coronavirus disease 2019 (COVID-19) vs patients with influenza. JAMA Neurol. 2020;77(11):1366–72.CrossRef
169.
170.
go back to reference Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of covid-19 in the young. N Engl J Med. 2020;382(20):e60.PubMedCrossRef Oxley TJ, Mocco J, Majidi S, Kellner CP, Shoirah H, Singh IP, et al. Large-vessel stroke as a presenting feature of covid-19 in the young. N Engl J Med. 2020;382(20):e60.PubMedCrossRef
171.
go back to reference Belani P, Schefflein J, Kihira S, Rigney B, Delman BN, Mahmoudi K, et al. COVID-19 Is an independent risk factor for acute ischemic stroke. Am J Neuroradiol. 2020;41(8):1361–4.PubMedCrossRefPubMedCentral Belani P, Schefflein J, Kihira S, Rigney B, Delman BN, Mahmoudi K, et al. COVID-19 Is an independent risk factor for acute ischemic stroke. Am J Neuroradiol. 2020;41(8):1361–4.PubMedCrossRefPubMedCentral
172.
go back to reference Wang A, Mandigo GK, Yim PD, Meyers PM, Lavine SD. Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics. J NeuroIntervent Surg. 2020;12(7):648–53.CrossRef Wang A, Mandigo GK, Yim PD, Meyers PM, Lavine SD. Stroke and mechanical thrombectomy in patients with COVID-19: technical observations and patient characteristics. J NeuroIntervent Surg. 2020;12(7):648–53.CrossRef
173.
go back to reference Majidi S, Fifi JT, Ladner TR, Lara-Reyna J, Yaeger KA, Yim B, et al. Emergent large vessel occlusion stroke during New York City’s COVID-19 outbreak: clinical characteristics and paraclinical findings. Stroke. 2020;51(9):2656–63.PubMedPubMedCentralCrossRef Majidi S, Fifi JT, Ladner TR, Lara-Reyna J, Yaeger KA, Yim B, et al. Emergent large vessel occlusion stroke during New York City’s COVID-19 outbreak: clinical characteristics and paraclinical findings. Stroke. 2020;51(9):2656–63.PubMedPubMedCentralCrossRef
174.
go back to reference Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, et al. SARS-CoV-2 and stroke in a New York healthcare system. Stroke. 2020;51(7):2002–11.PubMedCrossRef Yaghi S, Ishida K, Torres J, Mac Grory B, Raz E, Humbert K, et al. SARS-CoV-2 and stroke in a New York healthcare system. Stroke. 2020;51(7):2002–11.PubMedCrossRef
175.
go back to reference Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417–8.CrossRef Varga Z, Flammer AJ, Steiger P, Haberecker M, Andermatt R, Zinkernagel AS, et al. Endothelial cell infection and endotheliitis in COVID-19. The Lancet. 2020;395(10234):1417–8.CrossRef
176.
go back to reference Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine. 2020;24:100434.PubMedPubMedCentralCrossRef Rapkiewicz AV, Mai X, Carsons SE, Pittaluga S, Kleiner DE, Berger JS, et al. Megakaryocytes and platelet-fibrin thrombi characterize multi-organ thrombosis at autopsy in COVID-19: a case series. EClinicalMedicine. 2020;24:100434.PubMedPubMedCentralCrossRef
177.
go back to reference Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020;7(8):e575–82.PubMedPubMedCentralCrossRef Goshua G, Pine AB, Meizlish ML, Chang CH, Zhang H, Bahel P, et al. Endotheliopathy in COVID-19-associated coagulopathy: evidence from a single-centre, cross-sectional study. Lancet Haematol. 2020;7(8):e575–82.PubMedPubMedCentralCrossRef
178.
179.
go back to reference Xu J, Zhong S, Liu J, Li L, Li Y, Wu X, et al. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin Infect Dis. 2005;41(8):1089–96.PubMedCrossRef Xu J, Zhong S, Liu J, Li L, Li Y, Wu X, et al. Detection of severe acute respiratory syndrome coronavirus in the brain: potential role of the chemokine mig in pathogenesis. Clin Infect Dis. 2005;41(8):1089–96.PubMedCrossRef
180.
go back to reference Kim JE, Heo JH, Kim HO, Song SH, Park SS, Park TH, et al. Neurological complications during treatment of middle east respiratory syndrome. J Clin Neurol. 2017;13(3):227–33.PubMedPubMedCentralCrossRef Kim JE, Heo JH, Kim HO, Song SH, Park SS, Park TH, et al. Neurological complications during treatment of middle east respiratory syndrome. J Clin Neurol. 2017;13(3):227–33.PubMedPubMedCentralCrossRef
181.
go back to reference McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2007;81(2):813–21.PubMedCrossRef McCray PB, Pewe L, Wohlford-Lenane C, Hickey M, Manzel L, Shi L, et al. Lethal infection of K18-hACE2 mice infected with severe acute respiratory syndrome coronavirus. J Virol. 2007;81(2):813–21.PubMedCrossRef
182.
go back to reference St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ. Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J Virol. 2004;78(16):8824–34.PubMedPubMedCentralCrossRef St-Jean JR, Jacomy H, Desforges M, Vabret A, Freymuth F, Talbot PJ. Human respiratory coronavirus OC43: genetic stability and neuroinvasion. J Virol. 2004;78(16):8824–34.PubMedPubMedCentralCrossRef
183.
go back to reference Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264–75.PubMedPubMedCentralCrossRef Netland J, Meyerholz DK, Moore S, Cassell M, Perlman S. Severe acute respiratory syndrome coronavirus infection causes neuronal death in the absence of encephalitis in mice transgenic for human ACE2. J Virol. 2008;82(15):7264–75.PubMedPubMedCentralCrossRef
184.
go back to reference Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, et al. Middle east respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis. 2015;212(11):712–22. Li K, Wohlford-Lenane C, Perlman S, Zhao J, Jewell AK, Reznikov LR, et al. Middle east respiratory syndrome coronavirus causes multiple organ damage and lethal disease in mice transgenic for human dipeptidyl peptidase 4. J Infect Dis. 2015;212(11):712–22.
185.
go back to reference Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12:24.CrossRef Desforges M, Le Coupanec A, Dubeau P, Bourgouin A, Lajoie L, Dubé M, et al. Human coronaviruses and other respiratory viruses: underestimated opportunistic pathogens of the central nervous system? Viruses. 2019;12:24.CrossRef
186.
go back to reference Pellegrini L, Albecka A, Mallery DL, Kellner MJ, Paul D, Carter AP, et al. SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier. bioRxiv. 2020 Aug 21;2020.08.20.259937. Pellegrini L, Albecka A, Mallery DL, Kellner MJ, Paul D, Carter AP, et al. SARS-CoV-2 infects brain choroid plexus and disrupts the blood-CSF-barrier. bioRxiv. 2020 Aug 21;2020.08.20.259937.
187.
go back to reference Giri R, Shen Y, Stins M, Du YS, Schmidt AM, Stern D, et al. β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am J Physiol Cell Physiol. 2000;279(6):48–56.CrossRef Giri R, Shen Y, Stins M, Du YS, Schmidt AM, Stern D, et al. β-Amyloid-induced migration of monocytes across human brain endothelial cells involves RAGE and PECAM-1. Am J Physiol Cell Physiol. 2000;279(6):48–56.CrossRef
188.
go back to reference Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJA, Kraneveld AD. Exploring Braak’s hypothesis of parkinson’s disease. Front Neurol. 2017;8(FEB):1. Rietdijk CD, Perez-Pardo P, Garssen J, van Wezel RJA, Kraneveld AD. Exploring Braak’s hypothesis of parkinson’s disease. Front Neurol. 2017;8(FEB):1.
189.
go back to reference Butowt R, Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci. 2020;11:1200–3.PubMedCrossRef Butowt R, Bilinska K. SARS-CoV-2: olfaction, brain infection, and the urgent need for clinical samples allowing earlier virus detection. ACS Chem Neurosci. 2020;11:1200–3.PubMedCrossRef
190.
go back to reference Audrit KJ, Delventhal L, Aydin Ö, Nassenstein C. The nervous system of airways and its remodeling in inflammatory lung diseases. Cell Tissue Res. 2017;367:571–90.PubMedCrossRef Audrit KJ, Delventhal L, Aydin Ö, Nassenstein C. The nervous system of airways and its remodeling in inflammatory lung diseases. Cell Tissue Res. 2017;367:571–90.PubMedCrossRef
191.
go back to reference Driessen AK, Farrell MJ, Mazzone SB, McGovern AE. Multiple neural circuits mediating airway sensations: recent advances in the neurobiology of the urge-to-cough. Respir Physiol Neurobiol. 2016;1(226):115–20.CrossRef Driessen AK, Farrell MJ, Mazzone SB, McGovern AE. Multiple neural circuits mediating airway sensations: recent advances in the neurobiology of the urge-to-cough. Respir Physiol Neurobiol. 2016;1(226):115–20.CrossRef
192.
go back to reference Sorby-Adams AJ, Marcoionni AM, Dempsey ER, Woenig JA, Turner RJ. The role of neurogenic inflammation in blood-brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury. Int J Mol Sci. 2017;18:1788.PubMedCentralCrossRef Sorby-Adams AJ, Marcoionni AM, Dempsey ER, Woenig JA, Turner RJ. The role of neurogenic inflammation in blood-brain barrier disruption and development of cerebral oedema following acute central nervous system (CNS) injury. Int J Mol Sci. 2017;18:1788.PubMedCentralCrossRef
193.
go back to reference von Weyhern CH, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. Lancet. 2020;395:e109.CrossRef von Weyhern CH, Kaufmann I, Neff F, Kremer M. Early evidence of pronounced brain involvement in fatal COVID-19 outcomes. Lancet. 2020;395:e109.CrossRef
194.
go back to reference Politi LS, Salsano E, Grimaldi M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol. 2020;77:1028–9.PubMedCrossRef Politi LS, Salsano E, Grimaldi M. Magnetic resonance imaging alteration of the brain in a patient with coronavirus disease 2019 (COVID-19) and anosmia. JAMA Neurol. 2020;77:1028–9.PubMedCrossRef
195.
go back to reference Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11:995.PubMedCrossRef Baig AM, Khaleeq A, Ali U, Syeda H. Evidence of the COVID-19 virus targeting the CNS: tissue distribution, host-virus interaction, and proposed neurotropic mechanisms. ACS Chem Neurosci. 2020;11:995.PubMedCrossRef
198.
go back to reference Ramani A, Müller L, Ostermann PN, Gabriel E, Abida-Islam P, Müller-Schiffmann A, et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 2020;39(20):e106230.PubMedPubMedCentralCrossRef Ramani A, Müller L, Ostermann PN, Gabriel E, Abida-Islam P, Müller-Schiffmann A, et al. SARS-CoV-2 targets neurons of 3D human brain organoids. EMBO J. 2020;39(20):e106230.PubMedPubMedCentralCrossRef
199.
go back to reference Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021;218(3):e20202135.PubMedPubMedCentralCrossRef Song E, Zhang C, Israelow B, Lu-Culligan A, Prado AV, Skriabine S, et al. Neuroinvasion of SARS-CoV-2 in human and mouse brain. J Exp Med. 2021;218(3):e20202135.PubMedPubMedCentralCrossRef
200.
go back to reference Murray RS, Cai GY, Hoel K, Zhang JY, Soike KF, Cabirac GF. Coronavirus infects and causes demyelination in primate central nervous system. Virology. 1992;188(1):274–84.PubMedCrossRef Murray RS, Cai GY, Hoel K, Zhang JY, Soike KF, Cabirac GF. Coronavirus infects and causes demyelination in primate central nervous system. Virology. 1992;188(1):274–84.PubMedCrossRef
201.
go back to reference De Santis G. SARS-CoV-2: a new virus but a familiar inflammation brain pattern. Brain Behav Immunity. 2020;347(xxxx):1–2. De Santis G. SARS-CoV-2: a new virus but a familiar inflammation brain pattern. Brain Behav Immunity. 2020;347(xxxx):1–2.
202.
go back to reference Butler N, Pewe L, Trandem K, Perlman S. Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology. 2006;347(2):410–21.PubMedCrossRef Butler N, Pewe L, Trandem K, Perlman S. Murine encephalitis caused by HCoV-OC43, a human coronavirus with broad species specificity, is partly immune-mediated. Virology. 2006;347(2):410–21.PubMedCrossRef
203.
go back to reference Hachem M. SARS-CoV-2 journey to the brain with a focus on potential role of docosahexaenoic acid bioactive lipid mediators. Biochimie. 2021;184:95–103.PubMedPubMedCentralCrossRef Hachem M. SARS-CoV-2 journey to the brain with a focus on potential role of docosahexaenoic acid bioactive lipid mediators. Biochimie. 2021;184:95–103.PubMedPubMedCentralCrossRef
204.
go back to reference Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–9.PubMedPubMedCentralCrossRef Chen G, Wu D, Guo W, Cao Y, Huang D, Wang H, et al. Clinical and immunological features of severe and moderate coronavirus disease 2019. J Clin Invest. 2020;130(5):2620–9.PubMedPubMedCentralCrossRef
205.
go back to reference L C, HG L, W L, J L, K L, J S, et al. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 2020;43(0). L C, HG L, W L, J L, K L, J S, et al. [Analysis of clinical features of 29 patients with 2019 novel coronavirus pneumonia]. Zhonghua jie he he hu xi za zhi = Zhonghua jiehe he huxi zazhi = Chinese journal of tuberculosis and respiratory diseases. 2020;43(0).
206.
go back to reference Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan. China Clin Infect Dis. 2020;71(15):762–8.PubMedCrossRef Qin C, Zhou L, Hu Z, Zhang S, Yang S, Tao Y, et al. Dysregulation of immune response in patients with coronavirus 2019 (COVID-19) in Wuhan. China Clin Infect Dis. 2020;71(15):762–8.PubMedCrossRef
207.
go back to reference Tan M, Liu Y, Zhou R, Deng X, Li F, Liang K, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou. China Immunol. 2020;160(3):261–8.CrossRef Tan M, Liu Y, Zhou R, Deng X, Li F, Liang K, et al. Immunopathological characteristics of coronavirus disease 2019 cases in Guangzhou. China Immunol. 2020;160(3):261–8.CrossRef
208.
go back to reference Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395(10223):497–506.PubMedPubMedCentralCrossRef Huang C, Wang Y, Li X, Ren L, Zhao J, Hu Y, et al. Clinical features of patients infected with 2019 novel coronavirus in Wuhan China. Lancet. 2020;395(10223):497–506.PubMedPubMedCentralCrossRef
209.
go back to reference Liu F, Li L, Da XuM, Wu J, Luo D, Zhu YS, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370.PubMedPubMedCentralCrossRef Liu F, Li L, Da XuM, Wu J, Luo D, Zhu YS, et al. Prognostic value of interleukin-6, C-reactive protein, and procalcitonin in patients with COVID-19. J Clin Virol. 2020;127:104370.PubMedPubMedCentralCrossRef
210.
211.
go back to reference Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–9.PubMedPubMedCentralCrossRef Wang D, Hu B, Hu C, Zhu F, Liu X, Zhang J, et al. Clinical characteristics of 138 hospitalized patients with 2019 novel coronavirus-infected pneumonia in Wuhan, China. JAMA. 2020;323(11):1061–9.PubMedPubMedCentralCrossRef
212.
go back to reference Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.CrossRefPubMed Guan W, Ni Z, Hu Y, Liang W, Ou C, He J, et al. Clinical characteristics of coronavirus disease 2019 in China. N Engl J Med. 2020;382(18):1708–20.CrossRefPubMed
213.
go back to reference Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars Immunopathol. 2017;39:529–39.CrossRef Channappanavar R, Perlman S. Pathogenic human coronavirus infections: causes and consequences of cytokine storm and immunopathology. Seminars Immunopathol. 2017;39:529–39.CrossRef
214.
go back to reference Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2.PubMedPubMedCentralCrossRef Xu Z, Shi L, Wang Y, Zhang J, Huang L, Zhang C, et al. Pathological findings of COVID-19 associated with acute respiratory distress syndrome. Lancet Respir Med. 2020;8(4):420–2.PubMedPubMedCentralCrossRef
215.
go back to reference Chen J, Subbarao K. The immunobiology of SARS. Annu Rev Immunol. 2007;45:443–72.CrossRef Chen J, Subbarao K. The immunobiology of SARS. Annu Rev Immunol. 2007;45:443–72.CrossRef
216.
go back to reference Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81(16):8692–706.PubMedPubMedCentralCrossRef Cameron MJ, Ran L, Xu L, Danesh A, Bermejo-Martin JF, Cameron CM, et al. Interferon-mediated immunopathological events are associated with atypical innate and adaptive immune responses in patients with severe acute respiratory syndrome. J Virol. 2007;81(16):8692–706.PubMedPubMedCentralCrossRef
217.
go back to reference Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, et al. An interferon-γ-related cytokine storm in SARS patients. J Med Virol. 2005;75(2):185–94.PubMedCrossRef Huang KJ, Su IJ, Theron M, Wu YC, Lai SK, Liu CC, et al. An interferon-γ-related cytokine storm in SARS patients. J Med Virol. 2005;75(2):185–94.PubMedCrossRef
218.
219.
go back to reference Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis. 2004;189(4):648–51.PubMedCrossRef Li T, Qiu Z, Zhang L, Han Y, He W, Liu Z, et al. Significant changes of peripheral T lymphocyte subsets in patients with severe acute respiratory syndrome. J Infect Dis. 2004;189(4):648–51.PubMedCrossRef
220.
go back to reference Menachery VD, Eisfeld AJ, Schäfer A, Josset L, Sims AC, Proll S, et al. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. MBio. 2014;5(3):e01174-e1214.PubMedPubMedCentralCrossRef Menachery VD, Eisfeld AJ, Schäfer A, Josset L, Sims AC, Proll S, et al. Pathogenic influenza viruses and coronaviruses utilize similar and contrasting approaches to control interferon-stimulated gene responses. MBio. 2014;5(3):e01174-e1214.PubMedPubMedCentralCrossRef
221.
go back to reference Lau SKP, Lau CCY, Chan KH, Li CPY, Chen H, Jin DY, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 2013;94(PART 12):2679–90. Lau SKP, Lau CCY, Chan KH, Li CPY, Chen H, Jin DY, et al. Delayed induction of proinflammatory cytokines and suppression of innate antiviral response by the novel Middle East respiratory syndrome coronavirus: implications for pathogenesis and treatment. J Gen Virol 2013;94(PART 12):2679–90.
222.
go back to reference Yen Y-T, Liao F, Hsiao C-H, Kao C-L, Chen Y-C, Wu-Hsieh BA. Modeling the early events of severe acute respiratory syndrome coronavirus infection in vitro. J Virol. 2006;80(6):2684–93.PubMedPubMedCentralCrossRef Yen Y-T, Liao F, Hsiao C-H, Kao C-L, Chen Y-C, Wu-Hsieh BA. Modeling the early events of severe acute respiratory syndrome coronavirus infection in vitro. J Virol. 2006;80(6):2684–93.PubMedPubMedCentralCrossRef
223.
go back to reference Tynell J, Westenius V, Rönkkö E, Munster VJ, Melén K, Österlund P, et al. Middle east respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells. J Gen Virol. 2016;97(2):344–55.PubMedPubMedCentralCrossRef Tynell J, Westenius V, Rönkkö E, Munster VJ, Melén K, Österlund P, et al. Middle east respiratory syndrome coronavirus shows poor replication but significant induction of antiviral responses in human monocyte-derived macrophages and dendritic cells. J Gen Virol. 2016;97(2):344–55.PubMedPubMedCentralCrossRef
224.
go back to reference Zhou J, Chu H, Li C, Wong BHY, Cheng ZS, Poon VKM, et al. Active replication of middle east respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: Implications for pathogenesis. J Infect Dis. 2014;209(9):1331–42.PubMedCrossRef Zhou J, Chu H, Li C, Wong BHY, Cheng ZS, Poon VKM, et al. Active replication of middle east respiratory syndrome coronavirus and aberrant induction of inflammatory cytokines and chemokines in human macrophages: Implications for pathogenesis. J Infect Dis. 2014;209(9):1331–42.PubMedCrossRef
225.
go back to reference Law HKW, Chung YC, Hoi YN, Sin FS, Yuk OC, Luk W, et al. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005;106(7):2366–74.PubMedCrossRef Law HKW, Chung YC, Hoi YN, Sin FS, Yuk OC, Luk W, et al. Chemokine up-regulation in SARS-coronavirus-infected, monocyte-derived human dendritic cells. Blood. 2005;106(7):2366–74.PubMedCrossRef
226.
go back to reference Cheung CY, Poon LLM, Ng IHY, Luk W, Sia S-F, Wu MHS, et al. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005;79(12):7819–26.PubMedPubMedCentralCrossRef Cheung CY, Poon LLM, Ng IHY, Luk W, Sia S-F, Wu MHS, et al. Cytokine responses in severe acute respiratory syndrome coronavirus-infected macrophages in vitro: possible relevance to pathogenesis. J Virol. 2005;79(12):7819–26.PubMedPubMedCentralCrossRef
228.
go back to reference de Vries HE, Blom-Roosemalen MCM, van Oosten M, de Boer AG, van Berkel TJC, Breimer DD, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol. 1996;64(1):37–43.PubMedCrossRef de Vries HE, Blom-Roosemalen MCM, van Oosten M, de Boer AG, van Berkel TJC, Breimer DD, et al. The influence of cytokines on the integrity of the blood-brain barrier in vitro. J Neuroimmunol. 1996;64(1):37–43.PubMedCrossRef
229.
go back to reference Banks WA. The blood-brain barrier in neuroimmunology: Tales of separation and assimilation. Brain Behav Immunity. 2015;44:1–8.CrossRef Banks WA. The blood-brain barrier in neuroimmunology: Tales of separation and assimilation. Brain Behav Immunity. 2015;44:1–8.CrossRef
230.
go back to reference Banks W. Blood-Brain Barrier transport of cytokines: a mechanism for neuropathology. Curr Pharma Design. 2005;11(8):973–84.CrossRef Banks W. Blood-Brain Barrier transport of cytokines: a mechanism for neuropathology. Curr Pharma Design. 2005;11(8):973–84.CrossRef
232.
go back to reference Buttler L, Jordão MT, Fragas MG, Ruggeri A, Ceroni A, Michelini LC. Maintenance of blood-brain barrier integrity in hypertension: a novel benefit of exercise training for autonomic control. Front Physiol. 2017;8(DEC):1–14. Buttler L, Jordão MT, Fragas MG, Ruggeri A, Ceroni A, Michelini LC. Maintenance of blood-brain barrier integrity in hypertension: a novel benefit of exercise training for autonomic control. Front Physiol. 2017;8(DEC):1–14.
234.
go back to reference Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68(3):409–27.PubMedPubMedCentralCrossRef Bell RD, Winkler EA, Sagare AP, Singh I, LaRue B, Deane R, et al. Pericytes control key neurovascular functions and neuronal phenotype in the adult brain and during brain aging. Neuron. 2010;68(3):409–27.PubMedPubMedCentralCrossRef
235.
go back to reference Rosenberg GA, Cunningham LA, Wallace J, Alexander S, Estrada EY, Grossetete M, et al. Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res. 2001;893(1–2):104–12.PubMedCrossRef Rosenberg GA, Cunningham LA, Wallace J, Alexander S, Estrada EY, Grossetete M, et al. Immunohistochemistry of matrix metalloproteinases in reperfusion injury to rat brain: activation of MMP-9 linked to stromelysin-1 and microglia in cell cultures. Brain Res. 2001;893(1–2):104–12.PubMedCrossRef
236.
go back to reference Wei M, Li H, Shang Y, Zhou Z, Zhang J. Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury. Brain Res. 2014;17(1585):150–8.CrossRef Wei M, Li H, Shang Y, Zhou Z, Zhang J. Increased CD147 (EMMPRIN) expression in the rat brain following traumatic brain injury. Brain Res. 2014;17(1585):150–8.CrossRef
237.
go back to reference Pan P, Zhao H, Zhang X, Li Q, Qu J, Zuo S, et al. Cyclophilin a signaling induces pericyte-associated blood-brain barrier disruption after subarachnoid hemorrhage. J Neuroinflammation. 2020;17(1):16.PubMedPubMedCentralCrossRef Pan P, Zhao H, Zhang X, Li Q, Qu J, Zuo S, et al. Cyclophilin a signaling induces pericyte-associated blood-brain barrier disruption after subarachnoid hemorrhage. J Neuroinflammation. 2020;17(1):16.PubMedPubMedCentralCrossRef
238.
go back to reference Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD. Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Diabetologia. 2007;50(1):202–11.PubMedCrossRef Hawkins BT, Lundeen TF, Norwood KM, Brooks HL, Egleton RD. Increased blood-brain barrier permeability and altered tight junctions in experimental diabetes in the rat: contribution of hyperglycaemia and matrix metalloproteinases. Diabetologia. 2007;50(1):202–11.PubMedCrossRef
239.
go back to reference Kress BT, Iliff JJ, Xia M, Wang M, Wei Bs HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76(6):845–61.PubMedPubMedCentralCrossRef Kress BT, Iliff JJ, Xia M, Wang M, Wei Bs HS, Zeppenfeld D, et al. Impairment of paravascular clearance pathways in the aging brain. Ann Neurol. 2014;76(6):845–61.PubMedPubMedCentralCrossRef
240.
go back to reference Erickson MA, Banks WA. Age-associated changes in the immune system and blood–brain barrier functions. Int J Mol Sci. 2019;20(7):1632.PubMedCentralCrossRef Erickson MA, Banks WA. Age-associated changes in the immune system and blood–brain barrier functions. Int J Mol Sci. 2019;20(7):1632.PubMedCentralCrossRef
241.
go back to reference Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, Bell RD, et al. Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance. Proc Natl Acad Sci USA. 2013;110(36):14771–6.PubMedPubMedCentralCrossRef Singh I, Sagare AP, Coma M, Perlmutter D, Gelein R, Bell RD, et al. Low levels of copper disrupt brain amyloid-β homeostasis by altering its production and clearance. Proc Natl Acad Sci USA. 2013;110(36):14771–6.PubMedPubMedCentralCrossRef
242.
go back to reference Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model. J Clin Investig. 2005;115(11):3285–90.PubMedPubMedCentralCrossRef Cirrito JR, Deane R, Fagan AM, Spinner ML, Parsadanian M, Finn MB, et al. P-glycoprotein deficiency at the blood-brain barrier increases amyloid-β deposition in an Alzheimer disease mouse model. J Clin Investig. 2005;115(11):3285–90.PubMedPubMedCentralCrossRef
243.
go back to reference Yamazaki Y, Kanekiyo T. Blood-brain barrier dysfunction and the pathogenesis of alzheimer’s disease. Int J Mol Sci. 2017;18(9):1965.PubMedCentralCrossRef Yamazaki Y, Kanekiyo T. Blood-brain barrier dysfunction and the pathogenesis of alzheimer’s disease. Int J Mol Sci. 2017;18(9):1965.PubMedCentralCrossRef
244.
go back to reference Beck J, Horikawa I, Harris C. Cellular senescence: mechanisms, morphology, and mouse models. Vet Pathol. 2020;57:747–57.PubMedCrossRef Beck J, Horikawa I, Harris C. Cellular senescence: mechanisms, morphology, and mouse models. Vet Pathol. 2020;57:747–57.PubMedCrossRef
247.
go back to reference Montagne A, Zhao Z, Zlokovic B V. Alzheimer’s disease: a matter of blood–brain barrier dysfunction? J Exp Med 2017;jem.20171406. Montagne A, Zhao Z, Zlokovic B V. Alzheimer’s disease: a matter of blood–brain barrier dysfunction? J Exp Med 2017;jem.20171406.
248.
go back to reference Patching SG. Glucose Transporters at the blood-brain barrier: function, regulation and gateways for drug delivery. Mol Neurobiol. 2017;54(2):1046–77.PubMedCrossRef Patching SG. Glucose Transporters at the blood-brain barrier: function, regulation and gateways for drug delivery. Mol Neurobiol. 2017;54(2):1046–77.PubMedCrossRef
249.
go back to reference Qosa H, Abuasal BS, Romero IA, Weksler B, Couraud P-O, Keller JN, et al. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling. Neuropharmacology. 2014;79:668–78.PubMedPubMedCentralCrossRef Qosa H, Abuasal BS, Romero IA, Weksler B, Couraud P-O, Keller JN, et al. Differences in amyloid-β clearance across mouse and human blood-brain barrier models: kinetic analysis and mechanistic modeling. Neuropharmacology. 2014;79:668–78.PubMedPubMedCentralCrossRef
250.
go back to reference Deane R, Sagare A, Zlokovic B. The role of the cell surface LRP and soluble LRP in blood-brain barrier Aβ clearance in Alzheimer’s Disease. Curr Pharm Des. 2008;14(16):1601.PubMedPubMedCentralCrossRef Deane R, Sagare A, Zlokovic B. The role of the cell surface LRP and soluble LRP in blood-brain barrier Aβ clearance in Alzheimer’s Disease. Curr Pharm Des. 2008;14(16):1601.PubMedPubMedCentralCrossRef
252.
go back to reference McLean FH, Campbell FM, Langston RF, Sergi D, Resch C, Grant C, et al. A high-fat diet induces rapid changes in the mouse hypothalamic proteome. Nutr Metab. 2019;16(1):26.CrossRef McLean FH, Campbell FM, Langston RF, Sergi D, Resch C, Grant C, et al. A high-fat diet induces rapid changes in the mouse hypothalamic proteome. Nutr Metab. 2019;16(1):26.CrossRef
253.
go back to reference Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol. 2016;132(3):361–75.PubMedPubMedCentralCrossRef Baufeld C, Osterloh A, Prokop S, Miller KR, Heppner FL. High-fat diet-induced brain region-specific phenotypic spectrum of CNS resident microglia. Acta Neuropathol. 2016;132(3):361–75.PubMedPubMedCentralCrossRef
254.
go back to reference Kanoski SE, Zhang Y, Zheng W, Davidson TL. The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimer’s Dis. 2010;21(1):207–19.CrossRef Kanoski SE, Zhang Y, Zheng W, Davidson TL. The effects of a high-energy diet on hippocampal function and blood-brain barrier integrity in the rat. J Alzheimer’s Dis. 2010;21(1):207–19.CrossRef
255.
go back to reference Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE, Schwartz MW. Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes. 2013;62:2629–34.PubMedPubMedCentralCrossRef Thaler JP, Guyenet SJ, Dorfman MD, Wisse BE, Schwartz MW. Hypothalamic inflammation: marker or mechanism of obesity pathogenesis? Diabetes. 2013;62:2629–34.PubMedPubMedCentralCrossRef
257.
go back to reference Bogush M, Heldt NA, Persidsky Y. Blood brain barrier injury in diabetes : unrecognized effects on brain and cognition. J Neuroimmune Pharmacol. 2017;12:593–601.PubMedPubMedCentralCrossRef Bogush M, Heldt NA, Persidsky Y. Blood brain barrier injury in diabetes : unrecognized effects on brain and cognition. J Neuroimmune Pharmacol. 2017;12:593–601.PubMedPubMedCentralCrossRef
258.
go back to reference Gray SM, Barrett EJ. The blood-brain barrier in Diabetes Mellitus. Type 2 Diabetes and Dementia. Elsevier Inc.; 2018, p. 211–29. Gray SM, Barrett EJ. The blood-brain barrier in Diabetes Mellitus. Type 2 Diabetes and Dementia. Elsevier Inc.; 2018, p. 211–29.
259.
go back to reference Hadi HA, Al-Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manage. 2007;3(6):853. Hadi HA, Al-Suwaidi J. Endothelial dysfunction in diabetes mellitus. Vasc Health Risk Manage. 2007;3(6):853.
260.
go back to reference Setiadi A, Korim WS, Elsaafien K, Yao ST. The role of the blood–brain barrier in hypertension. Exp Physiol. 2018;103(3):337–42.PubMedCrossRef Setiadi A, Korim WS, Elsaafien K, Yao ST. The role of the blood–brain barrier in hypertension. Exp Physiol. 2018;103(3):337–42.PubMedCrossRef
261.
go back to reference Dinner S, Borkowski J, Stump-Guthier C, Ishikawa H, Tenenbaum T, Schroten H, et al. A choroid plexus epithelial cell-based model of the human blood-cerebrospinal fluid barrier to study bacterial infection from the basolateral side. J Vis Exp. 2016;2016(111):54061. Dinner S, Borkowski J, Stump-Guthier C, Ishikawa H, Tenenbaum T, Schroten H, et al. A choroid plexus epithelial cell-based model of the human blood-cerebrospinal fluid barrier to study bacterial infection from the basolateral side. J Vis Exp. 2016;2016(111):54061.
265.
267.
go back to reference Health England P. Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01. 2021. Health England P. Investigation of novel SARS-CoV-2 variant: variant of concern 202012/01. 2021.
269.
go back to reference Emary KRW, Golubchik T, Aley PK, Ariani C v., Angus BJ, Bibi S, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). SSRN Electronic Journal [Internet]. 2021. https://www.ssrn.com/abstract=3779160. Accessed 7 Feb 2021. Emary KRW, Golubchik T, Aley PK, Ariani C v., Angus BJ, Bibi S, et al. Efficacy of ChAdOx1 nCoV-19 (AZD1222) Vaccine Against SARS-CoV-2 VOC 202012/01 (B.1.1.7). SSRN Electronic Journal [Internet]. 2021. https://​www.​ssrn.​com/​abstract=​3779160. Accessed 7 Feb 2021.
271.
go back to reference Wu K, Werner AP, Moliva JI, Koch M, Choi A, Stewart-Jones GBE, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv: the preprint server for biology [Internet]. 2021 Jan 25;2021.01.25.427948. Available from: http://www.ncbi.nlm.nih.gov/pubmed/33501442. Accessed 7 Feb 2021. Wu K, Werner AP, Moliva JI, Koch M, Choi A, Stewart-Jones GBE, et al. mRNA-1273 vaccine induces neutralizing antibodies against spike mutants from global SARS-CoV-2 variants. bioRxiv: the preprint server for biology [Internet]. 2021 Jan 25;2021.01.25.427948. Available from: http://​www.​ncbi.​nlm.​nih.​gov/​pubmed/​33501442. Accessed 7 Feb 2021.
Metadata
Title
SARS-CoV-2: is there neuroinvasion?
Authors
Conor McQuaid
Molly Brady
Rashid Deane
Publication date
01-12-2021
Publisher
BioMed Central
Published in
Fluids and Barriers of the CNS / Issue 1/2021
Electronic ISSN: 2045-8118
DOI
https://doi.org/10.1186/s12987-021-00267-y

Other articles of this Issue 1/2021

Fluids and Barriers of the CNS 1/2021 Go to the issue