Top

Published in:

10-06-2022 | Septicemia | Original Article

Diabetes Exacerbates Sepsis-Induced Neuroinflammation and Brain Mitochondrial Dysfunction

Authors: Solange de Souza Stork, Marcos Hübner, Erica Biehl, Lucineia Gainski Danielski, Sandra Bonfante, Larissa Joaquim, Tais Denicol, Thaina Cidreira, Anita Pacheco, Erick Bagio, Everton Lanzzarin, Gabriela Bernades, Mariana Pacheco de Oliveira, Larissa Espindola da Silva, Josiel M. Mack, Franciane Bobinski, Gislaine Tezza Rezin, Tatiana Barichello, Emilio Luiz Streck, Fabricia Petronilho

Published in: Inflammation | Issue 6/2022

Abstract

Sepsis is a life-threatening organ dysfunction, which demands notable attention for its treatment, especially in view of the involvement of immunodepressed patients, as the case of patients with diabetes mellitus (DM), who constitute a population susceptible to develop infections. Thus, considering this endocrine pathology as an implicatory role on the immune system, the aim of this study was to show the relationship between this disease and sepsis on neuroinflammatory and neurochemical parameters. Levels of IL-6, IL-10, brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF), and mitochondrial respiratory chain complexes were evaluated in the hippocampus and prefrontal cortex 24 h after sepsis by cecal ligation and perforation (CLP) in Wistar rats induced to type 1 diabetes by alloxan (150 mg/kg). It was verified that diabetes implied immune function after 24 h of sepsis, since it contributed to the increase of the inflammatory process with higher production of IL-6 and decreased levels of IL-10 only in the hippocampus. In the same brain area, a several decrease in NGF level and activity of complexes I and II of the mitochondrial respiratory chain were observed. Thus, diabetes exacerbates neuroinflammation and results in mitochondrial impairment and downregulation of NGF level in the hippocampus after sepsis.

Trevelin, Silvia C., Daniela Carlos, Matteo Beretta, and Fernando Q. Cunha. 2017. Diabetes mellitus and sepsis: A challenging association. Shock 47: 276–287. https://doi.org/10.1097/SHK.0000000000000778.CrossRefPubMed

Evans, Laura, Andrew Rhodes, Waleed Alhazzani, Massimo Antonelli, Craig M Coopersmith, Craig French, Flávia R Machado, et al. 2021. Surviving sepsis campaign : international guidelines for management of sepsis and septic shock 2021. Intensive Care Medicine 47: 1181–1247. Springer Berlin Heidelberg. https://doi.org/10.1007/s00134-021-06506-y.

Singer, Mervyn, Clifford S. Deutschman, Christopherwarren Seymour, Manu Shankar-Hari, Djillali Annane, Michael Bauer, Rinaldo Bellomo, et al. 2016. The third international consensus definitions for sepsis and septic shock (sepsis-3). JAMA - Journal of the American Medical Association. American Medical Association. https://doi.org/10.1001/jama.2016.0287.

Sankowski, Roman, Simone Mader, and Sergio Iván Valdés-Ferrer. 2015. Systemic inflammation and the brain: Novel roles of genetic, molecular, and environmental cues as drivers of neurodegeneration. Frontiers in Cellular Neuroscience 9: 1–20. https://doi.org/10.3389/fncel.2015.00028.CrossRef

Biff, Daiane, Fabricia Petronilho, Larissa Constantino, Francieli Vuolo, Grettel J. Zamora-Berridi, Dhebora Mozena, and Dall’Igna, Larissa M. Comim, Joao Quevedo, Flavio Kapczinski, and Felipe Dal-Pizzol. 2013. Correlation of acute phase inflammatory and oxidative markers with long-term cognitive impairment in sepsis survivors rats. Shock 40: 45–48. https://doi.org/10.1097/SHK.0b013e3182959cfa.CrossRefPubMed

Dal-Pizzol, Felipe, Cristiane D. Tomasi, and Cristiane Ritter. 2014. Septic encephalopathy: Does inflammation drive the brain crazy? Revista Brasileira de Psiquiatria 36: 251–258. https://doi.org/10.1590/1516-4446-2013-1233.CrossRefPubMed

Danielski, Lucineia Gainski, Amanda Della Giustina, Marwa Badawy, Tatiana Barichello, João. Quevedo, Felipe Dal-Pizzol, and Fabrícia Petronilho. 2018. Brain barrier breakdown as a cause and consequence of neuroinflammation in sepsis. Molecular Neurobiology 55: 1045–1053. https://doi.org/10.1007/s12035-016-0356-7.CrossRefPubMed

Fink, Mitchell P., and Stephen O. Heard. 1990. Laboratory models of sepsis and septic shock. Journal of Surgical Research 49: 186–196. https://doi.org/10.1016/0022-4804(90)90260-9.

Michels, M., L.G. Danieslki, A. Vieira, D. Florentino, D. Dall’Igna, L. Galant, B. Sonai, et al. 2015. CD40-CD40 ligand pathway is a major component of acute neuroinflammation and contributes to long-term cognitive dysfunction after sepsis. Molecular Medicine 21. https://doi.org/10.2119/molmed.2015.0

10.

Rittirsch, D., M.S. Huber-Lang, M.A. Flierl, and P.A. Ward. 2009. Immunodesign of experimental sepsis by cecal ligation and puncture. Nature Protocols 4: 31–36. https://doi.org/10.1038/nprot.2008.214.CrossRefPubMedPubMedCentral

11.

Benedet, Joana, Kozuchovski Ferreira, Pereira Teodorak, and Martinelli Comim. 2011. Inhibition of brain citrate synthase activity in an animal model of sepsis. Revista Brasileira de terapia intensiva 23: 158–163. https://doi.org/10.1590/S0103-507X2011000200007.CrossRefPubMed

12.

Lima, Lea, Socorro Ferraz, and Marta Chagas Monteiro. 2010. Fatores de risco associados ao agravamento de sepse em pacientes em Unidade de Terapia Intensiva the Intensive Care Unit. Cadernos Saúde Coletiva 24: 388–396. https://doi.org/10.1590/1414-462X201600040091.CrossRef

13.

Koh, G.C.K.W., S.J. Peacock, T. Van Der Poll, and W.J. Wiersinga. 2012. The impact of diabetes on the pathogenesis of sepsis. European Journal of Clinical Microbiology & Infectious Diseases 31: 379–388. https://doi.org/10.1007/s10096-011-1337-4.CrossRef

14.

Mantzarlis, Konstantinos, Vasiliki Tsolaki, and Epaminondas Zakynthinos. 2017. Role of oxidative stress and mitochondrial dysfunction in sepsis and potential therapies. Oxidative Medicine and Cellular Longevity. Hindawi Limited. https://doi.org/10.1155/2017/5985209.

15.

Vieira, A., M. Michels, D. Florentino, A.A. Lauriano, L.G. Danielski, J.J. Fortunato, T. Barichello, D.-P. Felipe, J. Quevedo, and F. Petronilho. 2014. Increased on oxidative brain injury in the diabetic rats following sepsis. Synapse 68. https://doi.org/10.1002/syn.21753

16.

Kottaisamy, Chidhambara Priya Dharshini, Divya S. Raj, V. Prasanth Kumar, and Umamaheswari Sankaran. 2021. Experimental animal models for diabetes and its related complications-a review. Laboratory animal research 37. https://doi.org/10.1186/S42826-021-00101-4.

17.

Sun, Jian, Jingxiao Zhang, Jiakun Tian, Grazia Maria Virzì, Kumar Digvijay, Laura Cueto, Yongjie Yin, Mitchell H. Rosner, and Claudio Ronco. 2019. Mitochondria in sepsis-induced AKI. Journal of the American Society of Nephrology 30: 1151–1161. https://doi.org/10.1681/ASN.2018111126.CrossRefPubMedPubMedCentral

18.

Zhang, Hui, Yong Wen Feng, and Yong Ming Yao. 2018. Potential therapy strategy: targeting mitochondrial dysfunction in sepsis. Military Medical Research 5: 1–11. https://doi.org/10.1186/s40779-018-0187-0.

19.

Belenguer, Pascale, João M.N. Duarte, Patrícia F. Schuck, and Gustavo C. Ferreira. 2019. Mitochondria and the brain: bioenergetics and beyond. Neurotoxicity research 36: 219–238. https://doi.org/10.1007/S12640-019-00061-7.

20.

Shenoy, Santosh. 2020. Coronavirus (Covid-19) sepsis: revisiting mitochondrial dysfunction in pathogenesis, aging, inflammation, and mortality. Inflammation Research. Springer Science and Business Media Deutschland GmbH. https://doi.org/10.1007/s00011-020-01389-z.

21.

Wasyluk, Weronika, and Agnieszka Zwolak. 2021. Metabolic alterations in sepsis. Journal of Clinical Medicine 10: 1–18. https://doi.org/10.3390/jcm10112412.CrossRef

22.

Calvo-Ochoa, Erika, Karina Hernández-Ortega, Patricia Ferrera, Sumiko Morimoto, and Clorinda Arias. 2014. Short-term high-fat-and-fructose feeding produces insulin signaling alterations accompanied by neurite and synaptic reduction and astroglial activation in the rat hippocampus. Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism 34: 1001–1008. https://doi.org/10.1038/JCBFM.2014.48.

23.

Dutheil, Sophie, Kristie T. Ota, Eric S. Wohleb, Kurt Rasmussen, and Ronald S. Duman. 2016. High-fat diet induced anxiety and anhedonia: impact on brain homeostasis and inflammation. Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 41: 1874–1887. Neuropsychopharmacology. https://doi.org/10.1038/NPP.2015.357.

24.

Li, Yuanzhe, Huayan Zhao, Yalin Guo, Yongtao Duan, Yanjun Guo, and Xianfei Ding. 2021. Association of preadmission metformin use and prognosis in patients with sepsis and diabetes mellitus: a systematic review and meta-analysis. Frontiers in endocrinology 12: 811776. Frontiers Media S.A. https://doi.org/10.3389/fendo.2021.811776.

25.

Yao, Weifeng, Haofeng Liao, Mengya Pang, Lijie Pan, Yu Guan, Xiaolei Huang, Ziqing Hei, Chenfang Luo, and Mian Ge. 2022. Inhibition of the NADPH oxidase pathway reduces ferroptosis during septic renal injury in diabetic mice. Edited by Liang-Jun Yan. Oxidative medicine and cellular longevity 2022: 1193734. https://doi.org/10.1155/2022/1193734.

26.

Cassina, Adriana, and Rafael Radi. 1996. Differential inhibitory action of nitric oxide and peroxynitrite on mitochondrial electron transport. Archives of Biochemistry and Biophysics 328: 309–316. https://doi.org/10.1006/abbi.1996.0178.CrossRefPubMed

27.

Fischer, Johan C., Wim Ruitenbeek, Jan A. Berden, J.M. Frans Trijbels, Jacques H. Veerkamp, Ad.M. Stadhouders, Rob C.A.. Sengers, and Antoon J.M.. Janssen. 1985. Differential investigation of the capacity of succinate oxidation in human skeletal muscle. Clinica Chimica Acta 153: 23–36. https://doi.org/10.1016/0009-8981(85)90135-4.CrossRef

28.

Dal-Pizzol, Felipe, Cristiane Ritter, Omar J. Cassol-Jr, Gislaine T. Rezin, Fabrícia Petronilho, Alexandra I. Zugno, João. Quevedo, and Emilio L. Streck. 2010. Oxidative mechanisms of brain dysfunction during sepsis. Neurochemical Research 35: 1–12. https://doi.org/10.1007/s11064-009-0043-4.CrossRefPubMed

29.

Bermpohl, Daniela, Annett Halle, Dorette Freyer, Emilie Dagand, Johann S. Braun, Ingo Bechmann, Nicolas W.J.. Schröder, and Joerg R. Weber. 2005. Bacterial programmed cell death of cerebral endothelial cells involves dual death pathways. Journal of Clinical Investigation 115: 1607–1615. https://doi.org/10.1172/JCI23223.CrossRefPubMedPubMedCentral

30.

Cancelier, Ana Carolina, Fabricia Petronilho, Adalisa Reinke, Larissa Constantino, Roberta Machado, Cristiane Ritter, and Felipe Dal-Pizzol. 2009. Inflammatory and oxidative parameters in cord blood as diagnostic of early-onset neonatal sepsis: A case-control study. Pediatric critical care medicine : A journal of the Society of Critical Care Medicine and the World Federation of Pediatric Intensive and Critical Care Societies 10: 467–471. https://doi.org/10.1097/PCC.0b013e318198b0e3.CrossRef

31.

Bozza, Fernando A., Joana C. D’Avila, Cristiane Ritter, Romain Sonneville, Tarek Sharshar, and Felipe Dal-Pizzol. 2013. Bioenergetics, mitochondrial dysfunction, and oxidative stress in the pathophysiology of septic encephalopathy. Shock 39: 10–16. https://doi.org/10.1097/SHK.0b013e31828fade1.CrossRefPubMed

32.

Peleg, Anton Y., Thilak Weerarathna, James McCarthy, and Timothy M.E.. Davis. 2007. Common infections in diabetes: Pathogenesis, management and relationship to glycaemic control. Diabetes/Metabolism Research and Reviews 23: 3–13. https://doi.org/10.1002/dmrr.CrossRefPubMed

33.

Minelli, Lorivaldo, Andrei Bungart Nonino, Jaqueline Cantarelli Salmazo, Leandro Neme, and Marcelo Marcondes. 2003. Diabetes mellitus and cutaneous affections. Anais Brasileiros de Dermatologia 78: 735–747. https://doi.org/10.1590/s0365-05962003000600010.CrossRef

34.

Berbudi, Afiat, Nofri Rahmadika, Adi Imam Tjahjadi, and Rovina Ruslami. 2020. Type 2 diabetes and its impact on the immune system. Current Diabetes Reviews 16: 442–449. https://doi.org/10.2174/1573399815666191024085838.CrossRefPubMedPubMedCentral

35.

Frydrych, Lynn M., Fatemeh Fattahi, Katherine He, Peter A. Ward, Matthew J. Delano, and Matthew J. Delano. 2017. Diabetes and sepsis : Risk, recurrence, and ruination. Frontiers in Endocrinology 8: 1–22. https://doi.org/10.3389/fendo.2017.00271.CrossRef

36.

Plummer, Mark P., and Adam M. Deane. 2016. Dysglycemia and glucose control during sepsis. Clinics in Chest Medicine 37: 309–319. https://doi.org/10.1016/j.ccm.2016.01.010.CrossRefPubMed

37.

Feketeova, Eleonora, Zhifeng Li, Biju Joseph, Roshan Shah, Zoltan Spolarics, and Luis Ulloa. 2018. Dopaminergic control of inflammation and glycemia in sepsis and diabetes. Frontiers in Immunology 9: 1–12. https://doi.org/10.3389/fimmu.2018.00943.CrossRef

38.

Branco, Ricardo Garcia, Robert Charles Tasker, Pedro Celiny, Ramos Garcia, Jefferson Pedro Piva, and Lisandra Dias Xavier. 2007. Glycemic control and insulin therapy in sepsis and critical illness 83: 128–136. https://doi.org/10.2223/JPED.1710.

39.

Fabbri, Andrea, Giulio Marchesini, Barbara Benazzi, Alice Morelli, Danilo Montesi, Cesare Bini, and Stefano Giovanni Rizzo. 2020. Stress hyperglycemia and mortality in subjects with diabetes and sepsis. Critical Care Explorations 2: 1–6. https://doi.org/10.1097/CCE.0000000000000152.CrossRef

40.

Decarlo, Kristen, and Amisha Wallia. 2019. Inpatient management of T2DM and hyperglycemia in older adults. Current Diabetes Reports 19: 104.

41.

Akinosoglou, Karolina, Georgia Kapsokosta, Maria Mouktaroudi, Nikoletta Rovina, Vassileios Kaldis, Aggelos Stefos, and Evangelos Giamarellos-bourboulis. 2021. Diabetes on sepsis outcomes in non-ICU patients: a cohort study and review of the literature. Journal of Diabetes and Its Complications 35: 107765. Elsevier Inc. https://doi.org/10.1016/j.jdiacomp.2020.107765.

42.

Dewilde, Stephen, Tess Harris, Fay J. Hosking, and Derek G. Cook. 2018. Risk of infection in type 1 and type 2 diabetes compared with the general population : A matched cohort study. Diabetes Care 41: 513–521. https://doi.org/10.2337/dc17-2131/-/DC1.This.CrossRefPubMed

43.

Wasyluk, Weronika, Martyna Wasyluk, and Agnieszka Zwolak. 2021. Sepsis as a pan-endocrine illness — endocrine disorders in septic patients. Journal of Clinical Medicine 10: 1–14. https://doi.org/10.3390/jcm10102075.CrossRef

44.

Annane, Djillali, and Tarek Sharshar. 2015. Cognitive decline after sepsis. The Lancet Respiratory Medicine 3: 61–69. https://doi.org/10.1016/S2213-2600(14)70246-2.CrossRefPubMed

45.

Monje, Michelle L., Hiroki Toda, and Theo D. Palmer. 2003. Inflammatory blockade restores adult hippocampal neurogenesis. Science 302: 1760–1765. https://doi.org/10.1126/science.1088417.CrossRefPubMed

46.

Semmler, Alexander, Catherine Nichols Widmann, Thorsten Okulla, Horst Urbach, Markus Kaiser, Guido Widman, Florian Mormann, et al. 2013. Persistent cognitive impairment, hippocampal atrophy and EEG changes in sepsis survivors. Journal of Neurology, Neurosurgery and Psychiatry 84: 62–70. BMJ Publishing Group. https://doi.org/10.1136/jnnp-2012-302883.

47.

Schwalm, Mágada T, Matheus Pasquali, Samantha P Miguel, João Paulo, and A Santos. 2013. Acute brain inflammation and oxidative damage are related to long-term cognitive deficits and markers of neurodegeneration in sepsis-survivor rats: 13–18. https://doi.org/10.1007/s12035-013-8526-3.

48.

Lou, H.C. 1996. Etiology and pathogenesis of attention-deficit hyperactivity disorder (ADHD): Significance of prematurity and perinatal hypoxic-haemodynamic encephalopathy. Acta Paediatrica, International Journal of Paediatrics 85: 1266–1271. https://doi.org/10.1111/j.1651-2227.1996.tb13909.x.CrossRef

49.

Chousterman, Benjamin G, Filip K Swirski, and Georg F Weber. 2017. Cytokine storm and sepsis disease pathogenesis. Seminars in Immunopathology 39: 517–528. https://doi.org/10.1007/s00281-017-0639-8.

50.

Ishihara, Katsuhiko, and Toshio Hirano. 2002. IL-6 in autoimmune disease and chronic inflammatory proliferative disease. Cytokine & Growth Factor Reviews 13: 357–368. https://doi.org/10.1016/s1359-6101(02)00027-8.CrossRef

51.

Łukaszewicz, Marta, Barbara Mroczko, and Maciej Szmitkowski. 2007. Clinical significance of interleukin-6 (IL-6) as a prognostic factor of cancer disease. Polskie Archiwum Medycyny Wewnetrznej 117: 247–51. https://doi.org/10.20452/pamw.144.

52.

Maraschin, Jorge De, Nádia Murussi. Faria, Vanessa Witter, and Sandra Pinho Silveiro. 2010. Atualização Clínica Classificação do Diabete Melito. Arquivos Brasileiros de Cardiologia 95: 40–47.CrossRef

53.

Kellum, John A., Lan Kong, Mitchell P. Fink, Lisa A. Weissfeld, Donald M. Yealy, Michael R. Pinsky, Jonathan Fine, Alexander Krichevsky, Russell L. Delude, and Derek C. Angus. 2007. Understanding the inflammatory cytokine response in pneumonia and sepsis: Results of the Genetic and Inflammatory Markers of Sepsis (GenIMS) Study. Archives of Internal Medicine 167: 1655–1663. https://doi.org/10.1001/archinte.167.15.1655.Understanding.CrossRefPubMedPubMedCentral

54.

Kumar, Anil T., U. Sudhir, K. Punith, V.N. Rahul Kumar, Ravi Kumar, and Medha Y. Rao. 2008. Cytokine profile in elderly patients with sepsis. Indian Journal of Critical Care Medicine 13: 74–78. https://doi.org/10.4103/0972-5229.56052.CrossRef

55.

Feng, Mingchen, Tingting Sun, Yaxin Zhao, and Hui Zhang. 2016. Detection of serum interleukin-6/10/18 levels in sepsis and its clinical significance. Journal of Clinical Laboratory Analysis 30: 1037–1043. https://doi.org/10.1002/jcla.21977.CrossRefPubMedPubMedCentral

56.

Michels, Monique, Mariane Rocha, Abatti Pricila, Ávila. Andriele, Heloisa Borges, Celso Carvalho, Junior Diogo, et al. 2020. Characterization and modulation of microglial phenotypes in an animal model of severe sepsis. Journal of Cellular and Molecular Medicine 24: 88–97. https://doi.org/10.1111/jcmm.14606.CrossRefPubMed

57.

Nolasco, Eduardo Lima. 2013. Estudo da sepse experimental em animais diabéticos e sadios , tratados ou não com insulina. Universidade de São Paulo.

58.

Vieira, Andriele, Monique Michels, Drielly Florentino, André Antunes. Lauriano, Lucineia Gainski Danielski, Jucelia Jeremias Fortunato, Tatiana Barichello, Dal Pizzol Felipe, Joao Quevedo, and Fabricia Petronilho. 2014. Increased on oxidative brain injury in the diabetic rats following sepsis. Synapse (New York, N. Y.) 68: 410–418. https://doi.org/10.1002/syn.21753.CrossRef

59.

Forrest, Shelley L., Jillian J. Kril, and Glenda M. Halliday. 2019. Cellular and regional vulnerability in frontotemporal tauopathies. Acta Neuropathologica. Springer Verlag. https://doi.org/10.1007/s00401-019-02035-7.

60.

Vasic, Verica, and Mirko H H. Schmidt. 2017. Resilience and vulnerability to pain and inflammation in the hippocampus. International Journal of Molecular Sciences Review 18: 2–14. https://doi.org/10.3390/ijms18040739.CrossRef

61.

Petronilho, Fabricia. 2012. Marcadores inflamatórios e oxidativos em sangue de cordão umbilical como preditores de gravidade em sepse neonatal. Revista Brasileira de Terapia Intensiva 24: 30–34. https://doi.org/10.1590/S0103-507X2012000100005.CrossRefPubMed

62.

Asadullah, K., W. Sterry, and H.D. Volk. 2003. Interleukin-10 therapy — review of a new approach. Pharmacological Reviews 55: 241–269. https://doi.org/10.1124/pr.55.2.4.241.CrossRefPubMed

63.

Mohammadi, Mola, Homa Manaheji, Nader Maghsoudi, Samira Danyali, Mansoureh Baniasadi, and Jalal Zaringhalam. 2020. Microglia dependent BDNF and proBDNF can impair spatial memory performance during persistent inflammatory pain. Behavioural Brain Research 390: 112683. https://doi.org/10.1016/j.bbr.2020.112683.

64.

Florentino, Drielly, Amanda Della Giustina, Mariana Pereira de Souza Goldim, Lucineia Gainski Danielski, Aloir Neri de Oliveira Junior, Larissa Joaquim, Sandra Bonfante, et al. 2020. Early life neuroimmune challenge protects the brain after sepsis in adult rats. Neurochemistry International 135: 104712. Elsevier. https://doi.org/10.1016/j.neuint.2020.104712.

65.

Cassol-Jr, Omar J., Clarissa M. Comim, Larissa S. Constantino, Daniela V.F. Rosa, Luiz Alexandre V. Mango, Laura Stertz, Flávio Kapczinski, Marco A. Romano-Silva, João Quevedo, and Felipe Dal-Pizzol. 2011. Acute low dose of MK-801 prevents memory deficits without altering hippocampal DARPP-32 expression and BDNF levels in sepsis survivor rats. Journal of Neuroimmunology 230: 48–51. Elsevier B.V. https://doi.org/10.1016/j.jneuroim.2010.08.026.

66.

Martínez-Levy, Gabriela A., and Carlos S. Cruz-Fuentes. 2014. Genetic and epigenetic regulation of the brain-derived neurotrophic factor in the central nervous system. Yale Journal of Biology and Medicine 87: 173–186.PubMedPubMedCentral

67.

Lipsky, Robert H., and Ann M. Marini. 2007. Brain-derived neurotrophic factor in neuronal survival and behavior-related plasticity. Annals of the New York Academy of Sciences 1122: 130–143. https://doi.org/10.1196/annals.1403.009.CrossRefPubMed

68.

Minnone, Gaetana, Fabrizio De Benedetti, and Luisa Bracci-laudiero. 2017. NGF and its receptors in the regulation of inflammatory response. https://doi.org/10.3390/ijms18051028.

69.

Chandra, Mondal Amal, and Fatima Mahino. 2018. Direct and indirect evidences of BDNF and NGF as key modulators in depression: role of antidepressants treatment. International Journal of Neuroscience 129: 283–296. Taylor & Francis. https://doi.org/10.1080/00207454.2018.1527328.

70.

Espliguero, Gemma, Teresa Iglesias, and Angeles Rodrı. 2004. Expression of the neurotrophin receptor trkB is regulated by the cAMP / CREB pathway in neurons. Molecular and Cellular Neuroscience 26: 470–480. https://doi.org/10.1016/j.mcn.2004.03.007.CrossRefPubMed

71.

Venkatesan, Ramu, Eunhee Ji, and Sun Yeou Kim. 2015. Phytochemicals that regulate neurodegenerative disease by targeting neurotrophins : A comprehensive review. BioMed Research International 2015: 1–22. https://doi.org/10.1155/2015/814068.CrossRef

72.

Spencer, Jeremy P E, David Vauzour, and Catarina Rendeiro. 2009. Flavonoids and cognition : the molecular mechanisms underlying their behavioural effects. Archives of Biochemistry and Biophysics 492: 1–9. Elsevier Inc. https://doi.org/10.1016/j.abb.2009.10.003.

73.

Pugazhenthi, Subbiah, Ketaki Phansalkar, Gerald Audesirk, Anne West, and Leigh Cabell. 2006. Differential regulation of c-jun and CREB by acrolein and 4-hydroxynonenal. Free Radical Biology and Medicine 40: 21–34. https://doi.org/10.1016/j.freeradbiomed.2005.08.023.CrossRefPubMed

74.

Wu, Aiguo, Z.H.E. Ying, and Fernando Gomez-pinilla. 2004. Disability after traumatic brain injury in rats. Journal of Neurotrauma 21: 1457–1467.CrossRefPubMed

75.

Zou, Jian, and Fulton Crews. 2006. CREB and NF-κB transcription factors regulate sensitivity to excitotoxic and oxidative stress induced neuronal cell death. Cellular and Molecular Neurobiology 26: 385–405. https://doi.org/10.1007/s10571-006-9045-9.CrossRefPubMed

76.

Della Giustina, Amanda, Mariana Pereira Goldim, Lucinéia Gainski Danielski, Drielly Florentino, Khiany Mathias, Leandro Garbossa, Aloir Neri Oliveira Junior, et al. 2017. Alpha-lipoic acid attenuates acute neuroinflammation and long-term cognitive impairment after polymicrobial sepsis. Neurochemistry International 108: 436–447. Elsevier Ltd. https://doi.org/10.1016/j.neuint.2017.06.003.

77.

Goldstein, Benjamin I., Katelyn A. Collinger, Francis Lotrich, Anna L. Marsland, Mary-Kay. Gill, David A. Axelson, and Boris Birmaher. 2011. Preliminary findings regarding proinflammatory markers and brain-derived neurotrophic factor among adolescents with bipolar spectrum disorders. Journal of child and adolescent psychopharmacology 21: 479–484. https://doi.org/10.1089/cap.2011.0009.CrossRefPubMedPubMedCentral

78.

Barichello, Tatiana, Jaqueline S. Generoso, Lutiana R. Simões, Amanda V. Steckert, Ana Paula Moreira, Diogo Dominguini, Pâmela. Ferrari, et al. 2015. Folic acid prevented cognitive impairment in experimental pneumococcal meningitis. Journal of Neural Transmission 122: 643–651. https://doi.org/10.1007/s00702-014-1302-3.CrossRefPubMed

79.

Blondeau, Nicolas, Carine Nguemeni, David N. Debruyne, Marie Piens, Wu. Xuan, Hongna Pan, Hu. Xian Zhang, et al. 2009. Subchronic alpha-linolenic acid treatment enhances brain plasticity and exerts an antidepressant effect: A versatile potential therapy for stroke. Neuropsychopharmacology 34: 2548–2559. https://doi.org/10.1038/npp.2009.84.CrossRefPubMed

80.

Pudell, Claudia, Bianca A. Vicente, Ana M. Delattre, Bruno Carabelli, Marco A. Mori, Deborah Suchecki, Ricardo B. Machado, et al. 2014. Fish oil improves anxiety-like, depressive-like and cognitive behaviors in olfactory bulbectomised rats. European Journal of Neuroscience 39: 266–274. https://doi.org/10.1111/ejn.12406.CrossRefPubMed

81.

Bavaresco, Daniela V, Luciane B Ceretta, Karin M Gomes, and Graziela Amboni. 2016. Prejuízos cognitivos em Diabetes Mellitus: revisão da literatura. Prejuízos cognitivos em Diabetes Mellitus: revisão da literatura 5: 30–41. https://doi.org/10.18616/is.v5i1.2336.

82.

de Almeida-Pititto, Bianca, M. de Clineu, Almada Filho, and Maysa S. Cendoroglo. 2008. Déficit cognitivo: Mais uma complicação do diabetes melito? Arquivos Brasileiros de Endocrinologia & Metabologia 52: 1076–1083. https://doi.org/10.1590/s0004-27302008000700003.CrossRef

83.

Craft, Suzanne, and G. Stennis Watson. 2004. Insulin and neurodegenerative disease: Shared and specific mechanisms. Lancet Neurology 3: 169–178. https://doi.org/10.1016/S1474-4422(04)00681-7.CrossRefPubMed

84.

Cheng, Aiwu, Yan Hou, and Mark P. Mattson. 2010. Mitochondria and neuroplasticity. ASN Neuro 2: 243–256. https://doi.org/10.1042/AN20100019.CrossRef

85.

Marosi, Krisztina, and Mark P. Mattson. 2014. BDNF mediates adaptive brain and body responses to energetic challenges. Trends in Endocrinology and Metabolism 25: 89–98. Elsevier Ltd. https://doi.org/10.1016/j.tem.2013.10.006.

86.

Li, Longman, and Xiaobo Yang. 2018. The essential element manganese, oxidative stress, and metabolic diseases: links and interactions. Edited by Pan Chen. Oxidative Medicine and Cellular Longevity 2018: 7580707. Hindawi. https://doi.org/10.1155/2018/7580707.

87.

Candas, Demet, and Jian Jian Li. 2014. MnSOD in oxidative stress response-potential regulation via mitochondrial protein influx. Antioxidants & Redox Signaling 20: 1599–1617. https://doi.org/10.1089/ars.2013.5305.CrossRef

Title: Diabetes Exacerbates Sepsis-Induced Neuroinflammation and Brain Mitochondrial Dysfunction
Authors: Solange de Souza Stork
Marcos Hübner
Erica Biehl
Lucineia Gainski Danielski
Sandra Bonfante
Larissa Joaquim
Tais Denicol
Thaina Cidreira
Anita Pacheco
Erick Bagio
Everton Lanzzarin
Gabriela Bernades
Mariana Pacheco de Oliveira
Larissa Espindola da Silva
Josiel M. Mack
Franciane Bobinski
Gislaine Tezza Rezin
Tatiana Barichello
Emilio Luiz Streck
Fabricia Petronilho
Publication date: 10-06-2022
Publisher: Springer US
Keywords: Septicemia
Septicemia
Diabetes
Published in: Inflammation / Issue 6/2022
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI: https://doi.org/10.1007/s10753-022-01697-y

Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Reserve your place

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin

Prof. Florian Limbourg

Prof. Anoop Chauhan

Developed by: Springer Medicine

Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Please log in to get access to this content

Other articles of this Issue 6/2022

Correction to: Enhanced Responsive Formation of Extracellular Traps in Macrophages Previously Exposed to Porphyromonas gingivalis

Fenofibrate Downregulates NF-κB Signaling to Inhibit Pro-inflammatory Cytokine Secretion in Human THP-1 Macrophages and During Primary Biliary Cholangitis

Piperlongumin Improves Survival in the Mouse Model of Sepsis: Effect on Coagulation Factors and Lung Inflammation

Bifidobacterium bifidum and Bacteroides fragilis Induced Differential Immune Regulation of Enteric Glial Cells Subjected to Exogenous Inflammatory Stimulation

Therapeutic Potential of Curcumin in a Rat Model of Dextran Sulfate Sodium–Induced Ulcerative Colitis by Regulating the Balance of Treg/Th17 Cells

Saliva as a Potential Specimen to Monitor IL-6, TNF-α and IL-10 in COVID-19 Patients

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

At a glance: The STEP trials