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Journal of Neuroinflammation
Published in: Journal of Neuroinflammation 1/2019

Open Access 01-12-2019 | Stroke | Review

The spleen may be an important target of stem cell therapy for stroke

Authors: Zhe Wang, Da He, Ya-Yue Zeng, Li Zhu, Chao Yang, Yong-Juan Lu, Jie-Qiong Huang, Xiao-Yan Cheng, Xiang-Hong Huang, Xiao-Jun Tan

Published in: Journal of Neuroinflammation | Issue 1/2019

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Abstract

Stroke is the most common cerebrovascular disease, the second leading cause of death behind heart disease and is a major cause of long-term disability worldwide. Currently, systemic immunomodulatory therapy based on intravenous cells is attracting attention. The immune response to acute stroke is a major factor in cerebral ischaemia (CI) pathobiology and outcomes. Over the past decade, the significant contribution of the spleen to ischaemic stroke has gained considerable attention in stroke research. The changes in the spleen after stroke are mainly reflected in morphology, immune cells and cytokines, and these changes are closely related to the stroke outcomes. Autonomic nervous system (ANS) activation, release of central nervous system (CNS) antigens and chemokine/chemokine receptor interactions have been documented to be essential for efficient brain-spleen cross-talk after stroke. In various experimental models, human umbilical cord blood cells (hUCBs), haematopoietic stem cells (HSCs), bone marrow stem cells (BMSCs), human amnion epithelial cells (hAECs), neural stem cells (NSCs) and multipotent adult progenitor cells (MAPCs) have been shown to reduce the neurological damage caused by stroke. The different effects of these cell types on the interleukin (IL)-10, interferon (IFN), and cholinergic anti-inflammatory pathways in the spleen after stroke may promote the development of new cell therapy targets and strategies. The spleen will become a potential target of various stem cell therapies for stroke represented by MAPC treatment.
Literature
1.
Benjamin EJ, Blaha MJ, Chiuve SE, Cushman M, Das SR, Deo R, de Ferranti SD, Floyd J, Fornage M, Gillespie C, Isasi CR, Jiménez MC, Jordan LC, Judd SE, Lackland D, Lichtman JH, Lisabeth L, Liu S, Longenecker CT, Mackey RH, Matsushita K, Mozaffarian D, Mussolino ME, Nasir K, Neumar RW, Palaniappan L, Pandey DK, Thiagarajan RR, Reeves MJ, Ritchey M, Rodriguez CJ, Roth GA, Rosamond WD, Sasson C, Towfighi A, Tsao CW, Turner MB, Virani SS, Voeks JH, Willey JZ, Wilkins JT, Wu JH, Alger HM, Wong SS, Muntner P, American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Heart Disease and Stroke Statistics-2017 Update: A Report From the American Heart Association. Circulation. 2017;135(10):e146–603.PubMedPubMedCentralCrossRef
2.
Wei L, Wei ZZ, Jiang MQ, Mohamad O, Yu SP. Stem cell transplantation therapy for multifaceted therapeutic benefits after stroke. Prog Neurobiol. 2017;157:49–78.PubMedPubMedCentralCrossRef
3.
4.
Liu ZJ, Chen C, Li FW, Shen JM, Yang YY, Leak RK, et al. Splenic responses in ischemic stroke: new insights into stroke pathology. CNS Neurosci Ther. 2015;21(4):320–6.PubMedCrossRef
5.
Maya-Espinosa G, Collazo-Navarrete O, Millán-Aldaco D, Palomero-Rivero M, Guerrero-Flores G, Drucker-Colín R, et al. Mouse embryonic stem cell-derived cells reveal niches that support neuronal differentiation in the adult rat brain. Stem Cells. 2015;33(2):491–502.PubMedCrossRef
6.
Rosenblum S, Smith TN, Wang N, Chua JY, Westbroek E, Wang K, et al. BDNF pretreatment of human embryonic-derived neural stem cells improves cell survival and functional recovery after transplantation in hypoxic-ischemic stroke. Cell Transplant. 2015;24(12):2449–61.PubMedCrossRef
7.
Huang L, Wong S, Snyder EY, Hamblin MH, Lee JP. Human neural stem cells rapidly ameliorate symptomatic inflammation in early-stage ischemic-reperfusion cerebral injury. Stem Cell Res Ther. 2014;5(6):129.PubMedPubMedCentralCrossRef
8.
Chen L, Qiu R, Li L, He D, Lv H, Wu X, et al. The role of exogenous neural stem cells transplantation in cerebral ischemic stroke. J Biomed Nanotechnol. 2014;10(11):3219–30.PubMedCrossRef
9.
Cheng Y, Zhang J, Deng L, Johnson NR, Yu X, Zhang N, et al. Intravenously delivered neural stem cells migrate into ischemic brain, differentiate and improve functional recovery after transient ischemic stroke in adult rats. Int J Clin Exp Pathol. 2015;8(3):2928–36.PubMedPubMedCentral
10.
Wakao S, Kuroda Y, Ogura F, Shigemoto T, Dezawa M. Regenerative effects of mesenchymal stem cells: contribution of muse cells, a novel pluripotent stem cell type that resides in mesenchymal cells. Cell. 2012 Nov 8;1(4):1045–60.CrossRef
11.
Chen J, Li Y, Katakowski M, Chen X, Wang L, Lu D, et al. Intravenous bone marrow stromal cell therapy reduces apoptosis and promotes endogenous cell proliferation after stroke in female rat. J Neurosci Res. 2003;73(6):778–86.PubMedCrossRef
12.
Kondziolka D, Steinberg GK, Wechsler L, Meltzer CC, Elder E, Gebel J, et al. Neurotransplantation for patients with subcortical motor stroke: a phase 2 randomized trial. J Neurosurg. 2005;103(1):38–45.PubMedCrossRef
13.
Li Y, Chopp M, Chen J, Wang L, Gautam SC, Xu YX, et al. Intrastriatal transplantation of bone marrow nonhematopoietic cells improves functional recovery after stroke in adult mice. J Cereb Blood Flow Metab. 2000;20(9):1311–9.PubMedCrossRef
14.
Steinberg GK, Kondziolka D, Wechsler LR, Lunsford LD, Coburn ML, Billigen JB, et al. Clinical outcomes of transplanted modified bone marrow-derived mesenchymal stem cells in stroke: a phase 1/2a study. Stroke. 2016;47(7):1817–24.PubMedPubMedCentralCrossRef
15.
Otero L, Zurita M, Bonilla C, Aguayo C, Vela A, Rico MA, et al. Late transplantation of allogeneic bone marrow stromal cells improves neurologic deficits subsequent to intracerebral hemorrhage. Cytotherapy. 2011;13(5):562–71.PubMedCrossRef
16.
Wang L, Ji H, Li M, Zhou J, Bai W, Zhong Z, et al. Intrathecal administration of autologous CD34 positive cells in patients with past cerebral infarction: a safety study. ISRN Neurol. 2013;2013:128591.PubMedPubMedCentralCrossRef
17.
Danielyan L, Schäfer R, von Ameln-Mayerhofer A, Buadze M, Geisler J, Klopfer T, et al. Intranasal delivery of cells to the brain. Eur J Cell Biol. 2009;88(6):315–24.PubMedCrossRef
18.
Janowski M, Wagner D-C, Boltze J. Stem cell-based tissue replacement after stroke: factual necessity or notorious fiction? Stroke. 2015;46(8):2354–63.PubMedPubMedCentralCrossRef
19.
Eckert A, Huang L, Gonzalez R, Kim HS, Hamblin MH, Lee JP. Bystander effect fuels human induced pluripotent stem cell-derived neural stem cells to quickly attenuate early stage neurological deficits after stroke. Stem Cells Transl Med. 2015;4(7):841–51.PubMedPubMedCentralCrossRef
20.
Pendharkar AV, Chua JY, Andres RH, Wang N, Gaeta X, Wang H, et al. Biodistribution of neural stem cells after intravascular therapy for hypoxic-ischemia. Stroke. 2010;41(9):2064–70.PubMedPubMedCentralCrossRef
21.
Detante O, Valable S, de Fraipont F, Grillon E, Barbier EL, Moisan A, et al. Magnetic resonance imaging and fluorescence labeling of clinical-grade mesenchymal stem cells without impacting their phenotype: study in a rat model of stroke. Stem Cells Transl Med. 2012;1(4):333–41.PubMedPubMedCentralCrossRef
22.
Rosado-de-Castro PH, Schmidt Fda R, Battistella V, Lopes de Souza SA, Gutfilen B, Goldenberg RC, Kasai-Brunswick TH, Vairo L, Silva RM, Wajnberg E, Alvarenga Americano do Brasil PE, Gasparetto EL, Maiolino A, Alves-Leon SV, Andre C, Mendez-Otero R, Rodriguez de Freitas G, Barbosa da Fonseca LM. Biodistribution of bone marrow mononuclear cells after intra-arterial or intravenous transplantation in subacute stroke patients. RegenMed. 2013;8(2):145–55.
23.
24.
Gutiérrez-Fernández M, Rodríguez-Frutos B, Alvarez-Grech J, Vallejo-Cremades MT, Expósito-Alcaide M, Merino J, et al. Functional recovery after hematic administration of allogenic mesenchymal stem cells in acute ischemic stroke in rats. Neuroscience. 2011;175:394–405.PubMedCrossRef
25.
Li Y, Chen J, Wang L, Lu M, Chopp M. Treatment of stroke in rat with intracarotid administration of marrow stromal cells. Neurology. 2001;56(12):1666–72.PubMedCrossRef
26.
Banerjee S, Bentley P, Hamady M, Marley S, Davis J, Shlebak A, et al. Intra-arterial Immunoselected CD34+ stem cells for acute ischemic stroke. Stem Cells Transl Med. 2014;3(11):1322–30.PubMedPubMedCentralCrossRef
27.
Ohshima M, Taguchi A, Tsuda H, Sato Y, Yamahara K, Harada-Shiba M, et al. Intraperitoneal and intravenous deliveries are not comparable in terms of drug efficacy and cell distribution in neonatal mice with hypoxia-ischemia. Brain Dev. 2015;37(4):376–86.PubMedCrossRef
28.
Vahidy FS, Rahbar MH, Zhu H, Rowan PJ, Bambhroliya AB, Savitz SI. Systematic review and meta-analysis of bone marrow-derived mononuclear cells in animal models of ischemic stroke. Stroke. 2016;47:1632–9.PubMedPubMedCentralCrossRef
29.
Hess DC, Wechsler LR, Clark WM, Savitz SI, Ford GA, Chiu D, et al. Safety and efficacy of multipotent adult progenitor cells in acute ischaemic stroke (MASTERS): a randomised, double-blind, placebo-controlled, phase 2 trial. Lancet Neurol. 2017;16:360–8.PubMedCrossRef
30.
Bacigaluppi M, Pluchino S, Peruzzotti-Jametti L, Kilic E, Kilic U, Salani G, et al. Delayed post-ischaemic neuroprotection following systemic neural stem cell transplantation involves multiple mechanisms. Brain. 2009;132:2239–51.PubMedCrossRef
31.
Acosta SA, Tajiri N, Hoover J, Kaneko Y, Borlongan CV. Intravenous bone marrow stem cell grafts preferentially migrate to spleen and abrogate chronic inflammation in stroke. Stroke. 2015;46(9):2616–27.PubMedPubMedCentralCrossRef
32.
Vendrame M, Gemma C, Pennypacker KR, Bickford PC, Davis Sanberg C, Sanberg PR, et al. Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol. 2006;199(1):191–200.PubMedCrossRef
33.
Vendrame M, Cassady J, Newcomb J, Butler T, Pennypacker KR, Zigova T, et al. Infusion of human umbilical cord blood cells in a rat model of stroke dosedependently rescues behavioral deficits and reduces infarct volume. Stroke. 2004;35(10):2390–5.PubMedCrossRef
34.
Yan T, Venkat P, Ye X, Chopp M, Zacharek A, Ning R, et al. HUCBCs increase angiopoietin 1 and induce neurorestorative effects after stroke in T1DM rats. CNS Neurosci Ther. 2014;20(10):935–44.PubMedPubMedCentralCrossRef
35.
Schwarting S, Litwak S, Hao W, Bahr M, Weise J, Neumann H. Hematopoietic stem cells reduce postischemic inflammation and ameliorate ischemic brain injury. Stroke. 2008;39(10):2867–75.PubMedCrossRef
36.
Keimpema E, Fokkens MR, Nagy Z, Agoston V, Luiten PG, Nyakas C, et al. Early transient presence of implanted bone marrow stem cells reduces lesion size after cerebral ischaemia in adult rats. Neuropathol Appl Neurobiol. 2009;35(1):89–102.PubMedCrossRef
37.
Lee ST, Chu K, Jung KH, Kim SJ, Kim DH, Kang KM, et al. Anti-inflammatory mechanism of intravascular neural stem cell transplantation in haemorrhagic stroke. Brain. 2008;131(Pt 3):616–29.PubMedCrossRef
38.
Barone FC, Feuerstein GZ. Inflammatory mediators and stroke: new opportunities for novel therapeutics. J Cereb Blood Flow Metab. 1999;19(8):819–34.PubMedCrossRef
39.
del Zoppo G, Ginis I, Hallenbeck JM, Iadecola C, Wang X, Feuerstein GZ. Inflammation and stroke: putative role for cytokines, adhesion molecules and iNOS in brain response to ischemia. Brain Pathol. 2000;10(1):95–112.PubMedCrossRef
40.
41.
Li P, Mao L, Zhou G, Leak RK, Sun BL, Chen J, et al. Adoptive regulatory T cell therapy preserves systemic immune homeostasis following cerebral ischemia. Stroke. 2013;44(12):3509–15.PubMedPubMedCentralCrossRef
42.
Ren X, Akiyoshi K, Dziennis S, Vandenbark AA, Herson PS, Hurn PD, et al. Regulatory B-cells limit CNS inflammation and neurologic deficits in murine experimental stroke. J Neurosci. 2011;31(23):8556–63.PubMedPubMedCentralCrossRef
43.
Bodhankar S, Chen Y, Vandenbark AA, Murphy SJ, Offner H. Treatment of experimental stroke with IL-10-producing B-cells reduces infarct size and peripheral and CNS inflammation in wild-type B-cell-sufficient mice. Metab Brain Dis. 2014;29(1):59–73.PubMedCrossRef
44.
Luo Y, Zhou Y, Xiao W, Liang Z, Dai J, Weng X, et al. Interleukin-33 ameliorates ischemic brain injury in experimental stroke through promoting Th2 response and suppressing Th17 response. Brain Res. 2015;1597:86–94.PubMedCrossRef
45.
Kim E, Yang J, Beltran CD, Cho S. Role of spleen-derived monocytes/macrophages in acute ischemic brain injury. J Cereb Blood Flow Metab. 2014;34(8):1411–9.PubMedPubMedCentralCrossRef
46.
Yang B, Strong R, Sharma S, Brenneman M, Mallikarjunarao K, Xi X, et al. Therapeutic time window and dose response of autologous bone marrow mononuclear cells for ischemic stroke. J Neurosci Res. 2011;89(6):833–9.PubMedPubMedCentralCrossRef
47.
Becerra-Calixto A, Cardona-Gómez GP. The role of astrocytes in neuroprotection after brain Stroke_ potential in cell therapy. Front Mol Neurosci. 2017;10:88.PubMedPubMedCentralCrossRef
48.
Evans MA, Broughton BRS, Drummond GR, Ma H, Phan TG, Wallace EM, et al. Amnion epithelial cells - a novel therapy for ischemic stroke? Neural Regen Res. 2018;13(8):1346–9.PubMedPubMedCentralCrossRef
49.
Otero-Ortega L, Gómez de Frutos MC, Laso-García F, Rodríguez-Frutos B, Medina-Gutiérrez E, López JA, Vázquez J, Díez-Tejedor E, Gutiérrez-Fernández M. Exosomes promote restoration after an experimental animal model of intracerebral hemorrhage. J Cereb Blood Flow Metab. 2018;38(5):767–79.PubMedCrossRef
50.
Han Y, Seyfried D, Meng Y, Yang D, Schultz L, Chopp M, et al. Multipotent mesenchymal stromal cell-derived exosomes improve functional recovery after experimental intracerebral hemorrhage in the rat. J Neurosurg. 2018 Jul;20:1–11.
51.
52.
Woodruff TM, Thundyil J, Tang SC, Sobey CG, Taylor SM, Arumugam TV. Pathophysiology, treatment, and animal and cellular models of human ischemic stroke. Mol Neurodegener. 2011;6:11.PubMedPubMedCentralCrossRef
53.
Meisel C, Schwab JM, Prass K, Meisel A, Dirnagl U. Central nervous system injury-induced immune deficiency syndrome. Nat Rev Neurosci. 2005;6:775–86.PubMedCrossRef
54.
Famakin BM. The immune response to acute focal cerebral ischemia and associated post-stroke immunodepression: a focused review. Aging Dis. 2014;5(5):307–26.PubMedPubMedCentral
55.
Wattananit S, Tornero D, Graubardt N, Memanishvili T, Monni E, Tatarishvili J, et al. Monocyte-derived macrophages contribute to spontaneous long-term functional recovery after stroke in mice. J Neurosci. 2016;36:4182–95.PubMedCrossRefPubMedCentral
56.
Carden DL, Granger DN. Pathophysiology of ischaemia-reperfusion injury. J Pathol. 2000;190:255–66.PubMedCrossRef
57.
Peerschke EI, Yin W, Ghebrehiwet B. Complement activation on platelets: implications for vascular inflammation and thrombosis. Mol Immunol. 2010;47:2170–5.PubMedPubMedCentralCrossRef
58.
Hurley SD, Olschowka JA, O’Banion MK. Cyclooxygenase inhibition as a strategy to ameliorate brain injury. J Neurotrauma. 2002;19:1–15.PubMedCrossRef
59.
Minghetti L. Role of COX-2 in inflammatory and degenerative brain diseases. Subcell Biochem. 2007;42:127–41.PubMedCrossRef
60.
Iadecola C, Abe T, Kunz A, Hallembeck J. Cerebral ischemia and inflammation. In: Mohr JP, Wolf PA, Grotta JC, Moskowitz MA, Mayberg M, von Kummer R, editors. Stroke: pathophysiology, diagnosis and management. 5th ed. Philadelphia: Elsevier Health Sciences; 2011. p. 138–53.CrossRef
61.
Zhang Q, Raoof M, Chen Y, Sumi Y, Sursal T, Junger W, et al. Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature. 2010;464:104–7.PubMedPubMedCentralCrossRef
62.
63.
Caso JR, Pradillo JM, Hurtado O, Lorenzo P, Moro MA, Lizasoain I. Toll-like receptor 4 is involved in brain damage and inflammation after experimental stroke. Circulation. 2007;115:1599–608.PubMedCrossRef
64.
Savage CD, Lopez-Castejon G, Denes A, Brough D. NLRP3-Inflammasome activating DAMPs stimulate an inflammatory response in glia in the absence of priming which contributes to brain inflammation after injury. Front Immunol. 2012;3:288.PubMedPubMedCentralCrossRef
65.
Fann DY, Lee SY, Manzanero S, Chunduri P, Sobey CG, Arumugam TV. Pathogenesis of acute stroke and the role of inflammasomes. Ageing Res Rev. 2013;12:941–66.PubMedCrossRef
66.
Strbian D, Karjalainen-Lindsberg ML, Tatlisumak T, Lindsberg PJ. Cerebral mast cells regulate early ischemic brain swelling and neutrophil accumulation. J Cereb Blood Flow Metab. 2006;26:605–12.PubMedCrossRef
67.
68.
Huang J, Choudhri TF, Winfree CJ, McTaggart RA, Kiss S, Mocco J, et al. Postischemic cerebrovascular E-selectin expression mediates tissue injury in murine stroke. Stroke. 2000;31(12):3047–53.PubMedCrossRef
69.
Allan SM, Rothwell NJ. Cytokines and acute neurodegeneration. Nat Rev Neurosci. 2001;2(10):734–44 Review.PubMedCrossRef
70.
Burnstock G. Purinergic signalling and disorders of the central nervous system. Nat Rev Drug Discov. 2008;7:575–90.PubMedCrossRef
71.
Shichita T, Sugiyama Y, Ooboshi H, Sugimori H, Nakagawa R, Takada I, et al. Pivotal role of cerebral interleukin-17-producing gammadeltaT cells in the delayed phase of ischemic brain injury. Nat Med. 2009;15:946–50.PubMedCrossRef
72.
Meisel A, Meisel C, Harms H, Hartmann O, Ulm L. Predicting poststroke infections and outcome with blood-based immune and stress markers. Cerebrovasc Dis. 2012;33(6):580–8.PubMedCrossRef
73.
Hannawi Y, Hannawi B, Rao CP, Suarez JI, Bershad EM. Stroke-associated pneumonia: major advances and obstacles. Cerebrovasc Dis. 2013;35(5):430–43.PubMedCrossRef
74.
Kawanokuchi J, Shimizu K, Nitta A, Yamada K, Mizuno T, Takeuchi H, et al. Production and functions of IL-17 in microglia. J Neuroimmunol. 2008;194:54–61.PubMedCrossRef
75.
Morrison HW, Filosa JA. A quantitative spatiotemporal analysis of microglia morphology during ischemic stroke and reperfusion. J Neuroinflammation. 2013;10:4.PubMedPubMedCentralCrossRef
76.
Denes A, Vidyasagar R, Feng J, Narvainen J, McColl BW, Kauppinen RA, et al. Proliferating resident microglia after focal cerebral ischaemia in mice. J Cereb Blood Flow Metab. 2007;27:1941–53.PubMedCrossRef
77.
Villarreal A, Rosciszewski G, Murta V, Cadena V, Usach V, Dodes-Traian MM, et al. Isolation and characterization of ischemia-derived astrocytes (IDAs) with ability to transactivate quiescent astrocytes. Front Cell Neurosci. 2016;10:139.PubMedPubMedCentralCrossRef
78.
Liu Z, Chopp M. Astrocytes, therapeutic targets for neuroprotection and neurorestoration in ischemic stroke. Prog Neurobiol. 2016;144:103–20.PubMedCrossRef
79.
Fathali N, Ostrowski RP, Hasegawa Y, Lekic T, Tang J, Zhang JH. Splenic immune cells in experimental neonatal hypoxia-ischemia. Transl Stroke Res. 2013;4(2):208–19.PubMedCrossRef
80.
Li M, Li Z, Yao Y, Jin WN, Wood K, Liu Q, et al. Astrocyte-derived interleukin-15 exacerbates ischemic brain injury via propagation of cellular immunity. Proc Natl Acad Sci U S A. 2017;114(3):E396–405.PubMedCrossRef
81.
Cuadrado E, Jansen MH, Anink J, De Filippis L, Vescovi AL, Watts C, et al. Chronic exposure of astrocytes to interferon-α reveals molecular changes related to Aicardi-Goutieres syndrome. Brain. 2013;136(Pt 1):245–58.PubMedCrossRef
82.
Sims NR, Yew WP. Reactive astrogliosis in stroke: contributions of astrocytes to recovery of neurological function. Neurochem Int. 2017;107:88–103.PubMedCrossRef
83.
Hayakawa K, Esposito E, Wang X, Terasaki Y, Liu Y, Xing C, et al. Transfer of mitochondria from astrocytes to neurons after stroke. Nature. 2016;535(7613):551–5.PubMedPubMedCentralCrossRef
84.
Mattila OS, Strbian D, Saksi J, Pikkarainen TO, Rantanen V, Tatlisumak T, et al. Cerebral mast cells mediate blood-brain barrier disruption in acute experimental ischemic stroke through perivascular gelatinase activation. Stroke. 2011;42:3600–5.PubMedCrossRef
85.
Strbian D, Kovanen PT, Karjalainen-Lindsberg M-L, Tatlisumak T, Lindsberg PJ. An emerging role of mast cells in cerebral ischemia and hemorrhage. Ann Med. 2009;41:438–50.PubMedCrossRef
86.
Strbian D, Karjalainen-Lindsberg ML, Kovanen PT, Tatlisumak T, Lindsberg PJ. Mast cell stabilization reduces hemorrhage formation and mortality after administration of thrombolytics in experimental ischemic stroke. Circulation. 2007;116(4):411–8.PubMedCrossRef
87.
McKittrick CM, Lawrence CE, Carswell HV. Mast cells promote blood brain barrier breakdown and neutrophil infiltration in a mouse model of focal cerebral ischemia. J Cereb Blood Flow Metab. 2015;35(4):638–47.PubMedPubMedCentralCrossRef
88.
Fink SL, Cookson BT. Caspase-1-dependent pore formation during pyroptosis leads to osmotic lysis of infected host macrophages. Cell Microbiol. 2006;8:1812–25.PubMedCrossRef
89.
Schilling M, Besselmann M, Müller M, Strecker JK, Ringelstein EB, Kiefer R. Predominant phagocytic activity of resident microglia over hematogenous macrophages following transient focal cerebral ischemia: an investigation using green fluorescent protein transgenic bone marrow chimeric mice. Exp Neurol. 2005;196:290–7.PubMedCrossRef
90.
Nathan C, Ding A. Nonresolving inflammation. Cell. 2010;140:871882.
91.
Li S, Overman JJ, Katsman D, Kozlov SV, Donnelly CJ, Twiss JL, et al. An age-related sprouting transcriptome provides molecular control of axonal sprouting after stroke. Nat Neurosci. 2010;13:1496–504.PubMedPubMedCentralCrossRef
92.
Hayakawa K, Nakano T, Irie K, Higuchi S, Fujioka M, Orito K, et al. Inhibition of reactive astrocytes with fluorocitrate retards neurovascular remodeling and recovery after focal cerebral ischemia in mice. J Cereb Blood Flow Metab. 2010;30:871–82.PubMedCrossRef
93.
Hao Q, Chen Y, Zhu Y, Fan Y, Palmer D, Su H, et al. Neutrophil depletion decreases VEGF-induced focal angiogenesis in the mature mouse brain. J Cereb Blood Flow Metab. 2007;27:1853–60.PubMedCrossRef
94.
Vidale S, Consoli A, Arnaboldi M, Consoli D. Postischemic inflammation in acute stroke. J Clin Neurol. 2017 Jan;13(1):1–9.PubMedCrossRef
95.
Wang J, Yu L, Jiang C, Fu X, Liu X, Wang M, et al. Cerebral ischemia increases bone marrow CD4+CD25+FoxP3+ regulatory T cells in mice via signals from sympathetic nervous system. Brain Behav Immun. 2015;43:172–83.PubMedCrossRef
96.
Hori E, Hayakawa Y, Hayashi T, Hori S, Okamoto S, Shibata T, et al. Mobilization of pluripotent multilineage-differentiating stress-enduring cells in ischemic stroke. J Stroke Cerebrovasc Dis. 2016;25(6):1473–81.PubMedCrossRef
97.
Wang LL, Chen D, Lee J, Gu X, Alaaeddine G, Li J, et al. Mobilization of endogenous bone marrow derived endothelial progenitor cells and therapeutic potential of parathyroid hormone after ischemic stroke in mice. PLoS One. 2014;9(2):e87284.PubMedPubMedCentralCrossRef
98.
Shyu WC, Lin SZ, Yen PS, Su CY, Chen DC, Wang HJ, et al. Stromal cell-derived factor-1α promotes neuroprotection, angiogenesis, and mobilization/homing of bone marrow derived cells in stroke rats. J Pharmacol Exp Ther. 2008;324(2):834–49.PubMedCrossRef
99.
Gendron A, Teitelbaum J, Cossette C, Nuara S, Dumont M, Geadah D, et al. Temporal effects of left versus right middle cerebral artery occlusion on spleen lymphocyte subsets and mitogenic response in Wistar rats. Brain Res. 2002;955(1–2):85–97.PubMedCrossRef
100.
Prass K, Meisel C, Höflich C, Braun J, Halle E, Wolf T, et al. Stroke-induced immunodeficiency promotes spontaneous bacterial infections and is mediated by sympathetic activation reversal by poststroke T helper cell type 1-like immunostimulation. J Exp Med. 2003;198(5):725–36.PubMedPubMedCentralCrossRef
101.
Prass K, Ruscher K, Karsch M, Isaev N, Megow D, Priller J, et al. Desferrioxamine induces delayed tolerance against cerebral ischemia in vivo and in vitro. J Cereb Blood Flow Metab. 2002;22(5):520–5.PubMedCrossRef
102.
Offner H, Subramanian S, Parker SM, Wang C, Afentoulis ME, Lewis A, et al. Splenic atrophy in experimental stroke is accompanied by increased regulatory T cells and circlating macrophages. J Immunol. 2006;176(11):6523–31.PubMedCrossRef
103.
Braun JS, Prass K, Dirnagl U, Meisel A, Meisel C. Protection from brain damage and bacterial infection in murine stroke by the novel caspase-inhibitor Q-VD-OPH. Exp Neurol. 2007;206(2):183–91.PubMedCrossRef
104.
Ishibashi S, Maric D, Mou Y, Ohtani R, Ruetzler C, Hallenbeck JM. Mucosal tolerance to E-selectin promotes the survival of newly generated neuroblasts via regulatory T-cell induction after stroke in spontaneously hypertensive rats. J Cereb Blood Flow Metab. 2009;29(3):606–20.PubMedCrossRef
105.
106.
107.
van Zwam M, Huizinga R, Melief MJ, Wierenga-Wolf AF, van Meurs M, Voerman JS, Biber KP, Boddeke HW, Höpken UE, Meisel C, Meisel A, Bechmann I, Hintzen RQ, ‘t Hart BA, Amor S, Laman JD, Boven LA. Brain antigens in functionally distinct antigen-presenting cell populations in cervical lymph nodes in MS and EAE. J Mol Med (Berl). 2009;87(3):273–86.CrossRef
108.
Weller RO, Massey A, Kuo YM, Roher AE. Lymphatic drainage of the brain and the pathophysiology of neurological. Ann N Y Acad Sci. 2000;903:110–7.PubMedCrossRef
109.
Dirnagl U, Klehmet J, Braun JS, Harms H, Meisel C, Ziemssen T, et al. Stroke-induced immunodepression: experimental evidence and clinical relevance. Stroke. 2007;38(2 Suppl):770–3.PubMedCrossRef
110.
Schulte-Herbrüggen O, Quarcoo D, Meisel A, Meisel C. Differential affection of intestinal immune cell populations after cerebral Ischemiia in mice. Neuroimmunomodulation. 2009;16(3):213–8.PubMedCrossRef
111.
Mazmanian SK, Liu CH, Tzianabos AO, Kasper DL. An immunomodulatory molecule of symbiotic bacteria directs maturation of the host immune system. Cell. 2005;122:107–18.PubMedCrossRef
112.
Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M, et al. Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδT cells. Nat Med. 2016;22:516–23.PubMedPubMedCentralCrossRef
113.
Ajmo CT Jr, Vernon DO, Collier L, Hall AA, Garbuzova-Davis S, Willing A, et al. The spleen contributes to stroke-induced neurodegeneration. J Neurosci Res. 2008;86(10):2227–34.PubMedPubMedCentralCrossRef
114.
Jin R, Zhu X, Liu L, Nanda A, Granger DN, Li G. Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice. Stroke. 2013;44(4):1135–43.PubMedPubMedCentralCrossRef
115.
Lin JN, Lin CL, Lin MC, Lai CH, Lin HH, Yang CH, et al. Increased risk of hemorrhagic and ischemic strokes in patients with splenic injury and splenectomy: a Nationwide cohort study. Medicine (Baltimore). 2015;94(35):e1458.CrossRef
116.
Das M, Leonardo CC, Rangooni S, Mohapatra SS, Mohapatra S, Pennypacker KR. Lateral fluid percussion injury of the brain induces CCL20 inflammatory chemokine expression in rats. J Neuroinflammation. 2011;8:148.PubMedPubMedCentralCrossRef
117.
Li M, Li F, Luo C, Shan Y, Zhang L, Qian Z, et al. Immediate splenectomy decreases mortality and improves cognitive function of rats after severe traumatic brain injury. J Trauma. 2011;71(1):141–7.PubMedCrossRef
118.
Walker PA, Shah SK, Jimenez F, Gerber MH, Xue H, Cutrone R, et al. Intravenous multipotent adult progenitor cell therapy for traumatic brain injury: preserving the blood brain barrier via an interaction with splenocytes. Exp Neurol. 2010;225(2):341–52.PubMedPubMedCentralCrossRef
119.
Seifert HA, Leonardo CC, Hall AA, Rowe DD, Collier LA, Benkovic SA, et al. The spleen contributes to stroke induced neurodegeneration through interferon gamma signaling. Metab Brain Dis. 2012;27(2):131–41.PubMedPubMedCentralCrossRef
120.
Chauhan A, Al Mamun A, Spiegel G, Harris N, Zhu L, McCullough LD. Splenectomy protects aged mice from injury after experimental stroke. Neurobiol Aging. 2018;61:102–11.PubMedCrossRef
121.
Ran Y, Liu Z, Huang S, Shen J, Li F, Zhang W, et al. Splenectomy fails to provide long-term protection against ischemic stroke. Aging Dis. 2018;9(3):467–79.PubMedPubMedCentralCrossRef
122.
Ostrowski RP, Schulte RW, Nie Y, Ling T, Lee T, Manaenko A, et al. Acute splenic irradiation reduces brain injury in the rat focal ischemic stroke model. Transl Stroke Res. 2012;3:473–81.PubMedPubMedCentralCrossRef
123.
Ajmo CT Jr, Collier LA, Leonardo CC, Hall AA, Green SM, Womble TA, et al. Blockade of Adrenoreceptors inhibits the splenic response to stroke. Exp Neurol. 2009;218(1):47–55.PubMedPubMedCentralCrossRef
124.
Sahota P, Vahidy F, Nguyen C, Bui TT, Yang B, Parsha K, et al. Changes in spleen size in patients with acute ischemic stroke: a pilot observational study. Int J Stroke. 2013;8(2):60–7.PubMedCrossRef
125.
126.
Doycheva DM, Hadley T, Li L, Applegate RL, Zhang JH, Tang J. Anti-neutrophil antibody enhances the neuroprotective effects of G-CSF by decreasing number of neutrophils in hypoxic ischemic neonatal rat model. Neurobiol Dis. 2014;69:192–9.PubMedPubMedCentralCrossRef
127.
Price CJ, Menon DK, Peters AM. Cerebral neutrophil recruitment, histology, and outcome in acute ischemic stroke: an imaging-based study. Stroke. 2004;35:1659–64.PubMedCrossRef
128.
Chiu NL, Kaiser B, Nguyen YV, Welbourne S, Lall C, Cramer SC. The volume of the spleen and its correlates after acute stroke. J Stroke Cerebrovasc Dis. 2016;25(12):2958–61.PubMedPubMedCentralCrossRef
129.
Amantea D, Nappi G, Bernardi G, Bagetta G, Corasaniti MT. Post-ischemic brain damage: pathophysiology and role of inflammatory mediators. FEBS J. 2009;276:13–26.PubMedCrossRef
130.
Justicia C, Panés J, Solé S, Cervera A, Deulofeu R, Chamorro A, et al. Neutrophil infiltration increases matrix metalloproteinase-9 in the ischemic brain after occlusion/reperfusion of the middle cerebral artery in rats. J Cereb Blood Flow Metab. 2003;23:1430–40.PubMedCrossRef
131.
Sippel TR, Shimizu T, Strnad F, Traystman RJ, Herson PS, Waziri A. Arginase I release from activated neutrophils induces peripheral immunosuppression in a murine model of stroke. J Cereb Blood Flow Metab. 2015;35(10):1657–63.PubMedPubMedCentralCrossRef
132.
133.
Ma Y, Li Y, Jiang L, Wang L, Jiang Z, Wang Y, et al. Macrophage depletion reduced brain injury following middle cerebral artery occlusion in mice. J Neuroinflammation. 2016;13:38.PubMedPubMedCentralCrossRef
134.
Garcia-Bonilla L, Brea D, Benakis C, Lane DA, Murphy M, Moore J, et al. Endogenous protection from ischemic brain injury by preconditioned monocytes. J Neurosci. 2018;38(30):6722–36.PubMedPubMedCentralCrossRef
135.
136.
Hurn PD, Subramanian S, Parker SM, Afentoulis ME, Kaler LJ, Vandenbark AA, et al. T-and B-cell-deficient mice with experimental stroke have reduced lesion size and inflammation. J Cereb Blood Flow Metab. 2007;27:1798–805.PubMedCrossRef
137.
Yilmaz G, Arumugam TV, Stokes KY, Granger DN. Role of T lymphocytes and interferon-gamma in ischemic stroke. Circulation. 2006;113:2105–12.PubMedCrossRef
138.
Dotson AL, Zhu W, Libal N, Alkayed NJ, Offner H. Different immunological mechanisms govern protection from experimental stroke in young and older mice with recombinant TCR ligand therapy. Front Cell Neurosci. 2014;8:284.PubMedPubMedCentralCrossRef
139.
Zhang BJ, Men XJ, Lu ZQ, Li HY, Qiu W, Hu XQ. Splenectomy protects experimental rats from cerebral damage after stroke due to anti-inflammatory effects. Chin Med J. 2013;126(12):2354–60.PubMed
140.
Liesz A, Suri-Payer E, Veltkamp C, Doerr H, Sommer C, Rivest S, et al. Regulatory T cells are key cerebroprotective immunomodulators in acute experimental stroke. Nat Med. 2009;15:192–9.PubMedCrossRef
141.
142.
Na SY, Mracsko E, Liesz A, Hünig T, Veltkamp R. Amplification of regulatory T cells using a CD28 superagonist reduces brain damage after ischemic stroke in mice. Stroke. 2015;46(1):212–20.PubMedCrossRef
143.
Gu L, Xiong X, Zhang H, Xu B, Steinberg GK, Zhao H. Distinctive effects of T cell subsets in neuronal injury induced by cocultured splenocytes in vitro and by in vivo stroke in mice. Stroke. 2012;43(7):1941–6.PubMedPubMedCentralCrossRef
144.
Doyle KP, Quach LN, Solé M, Axtell RC, Nguyen TV, Soler-Llavina GJ, et al. B-lymphocyte-mediated delayed cognitive impairment following stroke. J Neurosci. 2015;35(5):2133–45.PubMedPubMedCentralCrossRef
145.
Bodhankar S, Chen Y, Vandenbark AA, Murphy SJ, Offner H. IL-10-producing B-cells limit CNS inflammation and infarct volume in experimental stroke. Metab Brain Dis. 2013;28:375–86.PubMedPubMedCentralCrossRef
146.
Chen Y, Bodhankar S, Murphy SJ, Vandenbark AA, Alkayed NJ, Offner H. Intrastriatal B-cell administration limits infarct size after stroke in B-cell deficient mice. Metab Brain Dis. 2012;27(4):487–93.PubMedPubMedCentralCrossRef
147.
Bodhankar S, Chen Y, Lapato A, Vandenbark AA, Murphy SJ, Saugstad JA, et al. Regulatory CD8(+) CD122 (+) T-cells predominate in CNS after treatment of experimental stroke in male mice with IL-10-secreting B-cells. Metab Brain Dis. 2015;30(4):911–24.PubMedCrossRef
148.
Gan Y, Liu Q, Wu W, Yin JX, Bai XF, Shen R, et al. Ischemic neurons recruit natural killer cells that accelerate brain infarction. Proc Natl Acad Sci U S A. 2014;111:2704–9.PubMedPubMedCentralCrossRef
149.
Zhang Y, Gao Z, Wang D, Zhang T, Sun B, Mu L, Li H, Wang G, et al. Accumulation of natural killer cells in ischemic brain tissues and the chemotactic effect of IP-10. J Neuroinflammation. 2014;11:79.PubMedPubMedCentralCrossRef
150.
Gelderblom M, Leypoldt F, Steinbach K, Behrens D, Choe CU, Siler DA, et al. Temporal and spatial dynamics of cerebral immune cell accumulation in stroke. Stroke. 2009;40:1849–57.PubMedCrossRef
151.
152.
Banchereau J, Briere F, Caux C, Davoust J, Lebecque S, Liu YJ, et al. Immunobiology of dendritic cells. Annu Rev Immunol. 2000;18:767–811.PubMedCrossRef
153.
Offner H, Subramanian S, Parker SM. Experimental stroke induces massive, rapid activation of the peripheral immune system. J Cereb Blood Flow Metab. 2006;26:654–65.PubMedCrossRef
154.
Seifert HA, Collier LA, Chapman CB, Benkovic SA, Willing AE, Pennypacker KR. Pro-inflammatory interferon gamma signaling is directly associated with stroke induced neurodegeneration. J NeuroImmune Pharmacol. 2014;9:679–89.PubMedPubMedCentralCrossRef
155.
Offner H, Vandenbark AA, Hurn PD. Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience. 2009;158(3):1098–111.PubMedCrossRef
156.
Vahidy FS, Parha KN, Rahbar MH, Lee M, Bui TT, Nguyen C, Barreto AD, Bambhroliya AB, Sahota P, Yang B, Aronowski J, Savitz SI. Acute splenic responses in patients with ischemic stroke and intracerebral hemorrhage. J Cereb Blood Flow Metab. 2016;36(6):1012–21.PubMedCrossRef
157.
Wang F, Shen Y, Tsuru E, Yamashita T, Baba N, Tsuda M, et al. Author information syngeneic transplantation of newborn splenocytes in a murine model of neonatal ischemia-reperfusion brain injury. J Matern Fetal Neonatal Med. 2015;28(7):842–7.PubMedCrossRef
158.
Wang J, Dotson AL, Murphy SJ, Offner H, Saugstad JA. Adoptive transfer of immune subsets prior to MCAO does not exacerbate stroke outcome in splenectomized mice. J Syst Integr Neurosci. 2015;1(1):20–8.PubMedPubMedCentralCrossRef
159.
Mignini F, Streccioni V, Amenta F. Autonomic innervation of immune organs and neuroimmune modulation. Auton Autacoid Pharmacol. 2003;23(1):1–25.PubMedCrossRef
160.
161.
Sörös P, Hachinski V. Cardiovascular and neurological causes of sudden death after ischaemic stroke. Lancet Neurol. 2012;11(2):179–88.PubMedCrossRef
162.
Bassi A, Colivicchi F, Santini M, Caltagirone C. Cardiac autonomic dysfunction and functional outcome after ischaemic stroke. Eur J Neurol. 2007;14(8):917–22.PubMedCrossRef
163.
Colivicchi F, Bassi A, Santini M, Caltagirone C. Prognostic implications of right-sided insular damage, cardiac autonomic derangement, and arrhythmias after acute ischemic stroke. Stroke. 2005;36(8):1710–5.PubMedCrossRef
164.
Korpelainen JT, Sotaniemi KA, Huikuri HV, Myllyä VV. Abnormal heart rate variability as a manifestation of autonomic dysfunction in hemispheric brain infarction. Stroke. 1996;27(11):2059–63.PubMedCrossRef
165.
Sander D, Winbeck K, Klingelhöfer J, Etgen T, Conrad B. Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke. Neurology. 2001;57(5):833–8.PubMedCrossRef
166.
Deng QW, Yang H, Yan FL, Wang H, Xing FL, Zuo L, et al. Blocking sympathetic nervous system reverses partially stroke-induced immunosuppression but does not aggravate functional outcome after experimental stroke in rats. Neurochem Res. 2016;41(8):1877–86.PubMedCrossRef
167.
Zierath D, Olmstead T, Stults A, Shen A, Kunze A, Becker KJ. Chemical Sympathectomy, but not adrenergic blockade, improves stroke outcome. J Stroke Cerebrovasc Dis. 2018;S1052-3057(18):30384–7.
168.
169.
Chamorro Á, Meisel A, Planas AM, Urra X, van de Beek D, Veltkamp R. The immunology of acute stroke. Nat Rev Neurol. 2012;8(7):401–10.PubMedCrossRef
170.
Mracsko E, Liesz A, Karcher S, Zorn M, Bari F, Veltkamp R. Differential effects of sympathetic nervous system and hypothalamic-pituitary-adrenal axis on systemic immune cells after severe experimental stroke. Brain Behav Immun. 2014;41:200–9.PubMedCrossRef
171.
Ma J, Zhang L, He G, Tan X, Jin X, Li C. Transcutaneous auricular vagus nerve stimulation regulates expression of growth differentiation factor 11 and activin-like kinase 5 in cerebral ischemia/reperfusion rats. J Neurol Sci. 2016 Oct;369:27–35.PubMedCrossRef
172.
Bonaz B, Sinniger V, Pellissier S. Anti-inflammatory properties of the vagus nerve: potential therapeutic implications of vagus nerve stimulation. J Physiol. 2016;594(20):5781–90.PubMedPubMedCentralCrossRef
173.
Zuo L, Shi L, Yan F. The reciprocal interaction of sympathetic nervous system and cAMP-PKA-NF-kB pathway in immune suppression after experimental stroke. Neurosci Lett. 2016;627:205–10.PubMedCrossRef
174.
Pongratz G, Melzer M, Straub RH. The sympathetic nervous system stimulates anti-inflammatory B cells in collagen-type II-induced arthritis. Ann Rheum Dis. 2012;71(3):432–9.PubMedCrossRef
175.
Pongratz G, Straub RH. The B cell, arthritis, and the sympathetic nervous system. Brain Behav Immun. 2010;24(2):186–92.PubMedCrossRef
176.
Rasouli J, Lekhraj R, Ozbalik M, Lalezari P, Casper D. Brain-spleen inflammatory coupling: a literature review. Einstein J Biol Med. 2011;27(2):74–7.PubMedPubMedCentralCrossRef
177.
Planas AM, Gómez-Choco M, Urra X, Gorina R, Caballero M, Chamorro Á. Brain-derived antigens in lymphoid tissue of patients with acute stroke. J Immunol. 2012;188:2156–63.PubMedCrossRef
178.
Tsuchida T, Parker KC, Turner RV, McFarland HF, Coligan JE, Biddison WE. Autoreactive CD8+ T-cell responses to human myelin protein-derived peptides. Proc Natl Acad Sci U S A. 1994;91:10859–63.PubMedPubMedCentralCrossRef
179.
Ortega SB, Noorbhai I, Poinsatte K, Kong X, Anderson A, Monson NL, et al. Stroke induces a rapid adaptive autoimmune response to novel neuronal antigens. Discov Med. 2015;19(106):381–92.PubMedPubMedCentral
180.
Ren X, Akiyoshi K, Grafe MR, Vandenbark AA, Hurn PD, Herson PS, et al. Myelin specific cells infiltrate MCAO lesions and exacerbate stroke severity. Metab Brain Dis. 2012;27(1):7–15.PubMedCrossRef
181.
Zierath D, Schulze J, Kunze A, Drogomiretskiy O, Nhan D, Jaspers B, et al. The immunologic profile of adoptively transferred lymphocytes influences stroke outcome of recipients. J Neuroimmunol. 2013;263(1–2):28–34.PubMedCrossRef
182.
183.
Dimitrijevic OB, Stamatovic SM, Keep RF, Andjelkovic AV. Absence of the chemokine receptor CCR2 protects against cerebral ischemia/reperfusion injury in mice. Stroke. 2007;38:1345–53.PubMedCrossRef
184.
Hill WD, Hess DC, Martin-Studdard A, Carothers JJ, Zheng J, Hale D, et al. SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury. J Neuropathol Exp Neurol. 2004;63(1):84–96.PubMedCrossRef
185.
Ruscher K, Kuric E, Liu Y, Walter HL, Issazadeh-Navikas S, Englund E, et al. Inhibition of CXCL12 signaling attenuates the postischemic immune response and improves functional recovery after stroke. J Cereb Blood Flow Metab. 2013;33(8):1225–34.PubMedPubMedCentralCrossRef
186.
Kim JS, Gautam SC, Chopp M, Zaloga C, Jones ML, Ward PA, et al. Expression of monocyte chemoattractant protein-1 and macrophage inflammatory protein-1 after focal cerebral ischemia in the rat. J Neuroimmunol. 1995;56(2):127–34.PubMedCrossRef
187.
Reichel CA, Rehberg M, Lerchenberger M, Berberich N, Bihari P, Khandoga AG, et al. Ccl2 and Ccl3 mediate neutrophil recruitment via induction of protein synthesis and generation of lipid mediators. Arterioscler Thromb Vasc Biol. 2009;29(11):1787–93.PubMedCrossRef
188.
Terao S, Yilmaz G, Stokes KY, Russell J, Ishikawa M, Kawase T, et al. Blood cell-derived RANTES mediates cerebral microvascular dysfunction, inflammation, and tissue injury after focal ischemia-reperfusion. Stroke. 2008;39(9):2560–70.PubMedPubMedCentralCrossRef
189.
Bazan JF, Bacon KB, Hardiman G, Wang W, Soo K, Rossi D, et al. A new class of membrane-bound chemokine with a CX3C motif. Nature. 1997;385(6617):640–4.PubMedCrossRef
190.
Dénes A, Ferenczi S, Halász J, Környei Z, Kovács KJ. Role of CX3CR1 (fractalkine receptor) in brain damage and inflammation induced by focal cerebral ischemia in mouse. J Cereb Blood Flow Metab. 2008;28(10):1707–21.PubMedCrossRef
191.
Domac FM, Misirli H. The role of neutrophils and interleukin-8 in acute ischemic stroke. Neurosciences (Riyadh). 2008;13(2):136–41.
192.
Herz J, Hagen SI, Bergmüller E, Sabellek P, Göthert JR, Buer J, et al. Exacerbation of ischemic brain injury in hypercholesterolemic mice is associated with pronounced changes in peripheral and cerebral immune responses. Neurobiol Dis. 2014;62:456–68.PubMedCrossRef
193.
Goldmacher GV, Nasser R, Lee DY, Yigit S, Rosenwasser R, Iacovitti L. Tracking transplanted bone marrow stem cells and their effects in the rat MCAO stroke model. PLoS One. 2013;8(3):e60049.PubMedPubMedCentralCrossRef
194.
Carrero R, Cerrada I, Lledó E, Dopazo J, García-García F, Rubio MP, et al. IL1β induces mesenchymal stem cells migration and leucocyte chemotaxis through NF-κB. Stem Cell Rev. 2012;8(3):905–16.PubMedCentralCrossRef
195.
Bai X, Xi J, Bi Y, Zhao X, Bing W, Meng X, et al. TNF-α promotes survival and migration of MSCs under oxidative stress via NF-κB pathway to attenuate intimal hyperplasia in vein grafts. J Cell Mol Med. 2017;21(9):2077–91.PubMedPubMedCentralCrossRef
196.
Golden JE, Shahaduzzaman M, Wabnitz A, Green S, Womble TA, Sanberg PR, et al. Human umbilical cord blood cells alter blood and spleen cell populations after stroke. Transl Stroke Res. 2012;3(4):491–9.PubMedPubMedCentralCrossRef
197.
Kadam SD, Chen H, Markowitz GJ, Raja S, George S, Verina T, et al. Systemic injection of CD34(+)-enriched human cord blood cells modulates poststroke neural and glial response in a sex-dependent manner in CD1 mice. Stem Cells Dev. 2015;24(1):51–66.PubMedCrossRef
198.
Peroni JF, Borjesson DL. Anti-inflammatory and immunomodulatory activities of stem cells. Vet Clin North Am Equine Pract. 2011;27(2):351–62.PubMedCrossRef
199.
Ulrich H, do Nascimento IC, Bocsi J, Tárnok A. Immunomodulation in stem cell differentiation into neurons and brain repair. Stem Cell Rev. 2015;11(3):474–86.CrossRef
200.
Racz GZ, Kadar K, Foldes A, Kallo K, Perczel-Kovach K, Keremi B, et al. Immunomodulatory and potential therapeutic role of mesenchymal stem cells in periodontitis. J Physiol Pharmacol. 2014;65(3):327–39.PubMed
201.
Zhang R, Liu Y, Yan K, Chen L, Chen XR, Li P, et al. Anti-inflammatory and immunomodulatory mechanisms of mesenchymal stem cell transplantation in experimental traumatic brain injury. J Neuroinflammation. 2013;10:106.PubMedPubMedCentral
202.
Dorronsoro A, Ferrin I, Salcedo JM, Jakobsson E, Fernández-Rueda J, Lang V, et al. Human mesenchymal stromal cells modulate T-cell responses through TNF-α-mediated activation of NF-κB. Eur J Immunol. 2014;44(2):480–8.PubMedCrossRef
203.
Prockop DJ, Oh JY. Mesenchymal stem/stromal cells (MSCs): role as guardians of inflammation. Mol Ther. 2012;20(1):14–20.PubMedCrossRef
204.
Gao S, Mao F, Zhang B, Zhang L, Zhang X, Wang M, et al. Mouse bone marrow-derived mesenchymal stem cells induce macrophage M2 polarization through the nuclear factor-κB and signal transducer and activator of transcription 3 pathways. Exp Biol Med (Maywood). 2014;239(3):366–75.CrossRef
205.
Evans MA, Lim R, Kim HA, Chu HX, Gardiner-Mann CV, Taylor KWE, Kwan W, Teo L, Bourne JA, Neumann S, Young S, Gowing EK, Drummond GR, Clarkson AN, Wallace EM, Sobey CG, Broughton BRS, et al. Acute or delayed systemic administration of human amnion epithelial cells improves outcomes in experimental stroke. Stroke. 2018;49(3):700–9.PubMedCrossRef
206.
Spera PA, Ellison JA, Feuerstein GZ, Barone FC. IL-10 reduces rat brain injury following focal stroke. Neurosci Lett. 1998;251(3):189–92.PubMedCrossRef
207.
Conway SE, Roy-O'Reilly M, Friedler B, Staff I, Fortunato G, McCullough LD. Sex differences and the role of IL-10 in ischemic stroke recovery. Biol Sex Differ. 2015;6:17.PubMedPubMedCentralCrossRef
208.
Wang Z, Zhou Y, Yu Y, He K, Cheng LM. Lipopolysaccharide Preconditioning Increased the Level of Regulatory B cells in the Spleen after Acute Ischaemia/Reperfusion in Mice. Brain Res. 2018;(18):30293–2.
209.
Yang H, Zhang A, Zhang Y, Ma S, Wang C. Resveratrol pretreatment protected against cerebral ischemia/reperfusion injury in rats via expansion of T regulatory cells. J Stroke Cerebrovasc Dis. 2016;25(8):1914–21.PubMedCrossRef
210.
211.
Dhib-Jalbut S, Marks S. Interferon-beta mechanisms of action in multiple sclerosis. Neurology. 2010;74(Suppl 1):S17–24.PubMedCrossRef
212.
Liu H, Xin L, Chan BP, Teoh R, Tang BL, Tan YH. Interferon-beta administration confers a beneficial outcome in a rabbit model of thromboembolic cerebral ischemia. Neurosci Lett. 2002;327:146–8.PubMedCrossRef
213.
Veldhuis WB, Derksen JW, Floris S, Van Der Meide PH, De Vries HE, Schepers J, et al. Interferon-beta blocks infiltration of inflammatory cells and reduces infarct volume after ischemic stroke in the rat. J Cereb Blood Flow Metab. 2003;23:1029–39.PubMedCrossRef
214.
Marsh B, Stevens SL, Packard AE, Gopalan B, Hunter B, Leung PY, et al. Systemic lipopolysaccharide protects the brain from ischemic injury by reprogramming the response of the brain to stroke: a critical role for IRF3. J Neurosci. 2009;29:9839–49.PubMedPubMedCentralCrossRef
215.
Inácio AR, Liu Y, Clausen BH, Svensson M, Kucharz K, Yang Y, et al. Endogenous IFN-β signaling exerts anti-inflammatory actions in experimentally induced focal cerebral ischemia. J Neuroinflammation. 2015;12:211.PubMedPubMedCentralCrossRef
216.
217.
Jung WC, Levesque JP, Ruitenberg MJ. It takes nerve to fight back: the significance of neural innervation of the bone marrow and spleen for immune function. Semin Cell Dev Biol. 2017;61:60–70.PubMedCrossRef
218.
219.
Bellinger DL, Lorton D. Autonomic regulation of cellular immune function. Auton Neurosci. 2014;182:15–41.PubMedCrossRef
220.
Elenkov IJ, Wilder RL, Chrousos GP, Vizi ES. The sympathetic nerve--an integrative interface between two supersystems: the brain and the immune system. Pharmacol Rev. 2000;52(4):595–638.PubMed
221.
Lorton D, Bellinger DL. Molecular mechanisms underlying β-adrenergic receptor-mediated cross-talk between sympathetic neurons and immune cells. Int J Mol Sci. 2015;16(3):5635–65.PubMedPubMedCentralCrossRef
222.
223.
Bellinger DL, Felten SY, Lorton D, Felten DL. Origin of noradrenergic innervation of the spleen in rats. Brain Behav Immun. 1989;3(4):291–311.PubMedCrossRef
224.
Rosas-Ballina M, Olofsson PS, Ochani M, Valdés-Ferrer SI, Levine YA, Reardon C, et al. Acetylcholine-synthesizing T cells relay neural signals in a vagus nerve circuit. Science. 2011;334(6052):98–101.PubMedPubMedCentralCrossRef
225.
Peña G, Cai B, Ramos L, Vida G, Deitch EA, Ulloa L. Cholinergic regulatory lymphocytes re-establish neuromodulation of innate immune responses in sepsis. J Immunol. 2011;187(2):718–25.PubMedCrossRef
226.
Vida G, Peña G, Kanashiro A, Thompson-Bonilla Mdel R, Palange D, Deitch EA, et al. β2-Adrenoreceptors of regulatory lymphocytes are essential for vagal neuromodulation of the innate immune system. FASEB J. 2011;25(12):4476–85.PubMedPubMedCentralCrossRef
227.
Vida G, Peña G, Deitch EA, Ulloa L. α7-cholinergic receptor mediates vagal induction of splenic norepinephrine. J Immunol. 2011;186(7):4340–6.PubMedCrossRef
228.
Guan YZ, Jin XD, Guan LX, Yan HC, Wang P, Gong Z, et al. Ncotine inhibits microglial proliferation and is neuroprotective in global ischemia rats. Mol Neurobiol. 2015;51(3):1480–8.PubMedCrossRef
229.
Han Z, Shen F, He Y, Degos V, Camus M, Maze M, et al. Activation of α-7 nicotinic acetylcholine receptor reduces ischemic stroke injury through reduction of pro-inflammatory macrophages and oxidative stress. PLoS One. 2014;9(8):e105711.PubMedPubMedCentralCrossRef
230.
Parada E, Egea J, Buendia I, Negredo P, Cunha AC, Cardoso S, et al. The microglial α7-acetylcholine nicotinic receptor is a key element in promoting neuroprotection by inducing heme oxygenase-1 via nuclear factor erythroid-2-related factor 2. Antioxid Redox Signal. 2013;19(11):1135–48.PubMedPubMedCentralCrossRef
231.
Sun F, Jin K, Uteshev VV. A type-II positive allosteric modulator of α7 nAChRs reduces brain injury and improves neurological function after focal cerebral ischemia in rats. PLoS One. 2013;8(8):e73581.PubMedPubMedCentralCrossRef
232.
Sun F, Johnson SR, Jin K, Uteshev VV. Boosting endogenous resistance of brain to ischemia. Mol Neurobiol. 2017;54(3):2045–59.PubMedCrossRef
233.
Mays RW. Clinical development of MultiStem® for treatment of injuries and diseases of the central nervous system. In: Hess DC, editor. Cell therapy for brain injury. Switzerland: Springer International; 2015. p. 47–64.CrossRef
234.
Fischer UM, Harting MT, Jimenez F, Monzon-Posadas WO, Xue H, Savitz SI, et al. Pulmonary passage is a major obstacle for intravenous stem cell delivery: the pulmonary first-pass effect. Stem Cells Dev. 2009;18(5):683–92.PubMedCrossRef
235.
Roobrouck VD, Clavel C, Jacobs SA, Ulloa-Montoya F, Crippa S, Sohni A, et al. Differentiation potential of human postnatal mesenchymal stem cells, mesoangioblasts, and multipotent adult progenitor cells reflected in their transcriptome and partially influenced by the culture conditions. Stem Cells. 2011;29(5):871–82.PubMedCrossRef
236.
Boozer S, Lehman N, Lakshmipathy U, Love B, Raber A, Maitra A, et al. Global characterization and genomic stability of human MultiStem, a multipotent adult progenitor cell. J Stem Cells. 2009;4(1):17–28.PubMed
237.
Aranda P, Agirre X, Ballestar E, Andreu EJ, Román-Gómez J, Prieto I, et al. Epigenetic signatures associated with different levels of differentiation potential in human stem cells. PLoS One. 2009;4(11):e7809.PubMedPubMedCentralCrossRef
238.
Burrows GG, Van’t Hof W, Newell LF, Reddy A, Wilmarth PA, David LL, et al. Dissection of the human multipotent adult progenitor cell secretome by proteomic analysis. Stem Cells Transl Med. 2013;2(10):745–57.PubMedPubMedCentralCrossRef
239.
Bedi SS, Hetz R, Thomas C, Smith P, Olsen AB, Williams S, et al. Intravenous multipotent adult progenitor cell therapy attenuates activated microglial/macrophage response and improves spatial learning after traumatic brain injury. Stem Cells Transl Med. 2013;2(12):953–60.PubMedPubMedCentralCrossRef
240.
Walker PA, Bedi SS, Shah SK, Jimenez F, Xue H, Hamilton JA, et al. Intravenous multipotent adult progenitor cell therapy after traumatic brain injury: modulation of the resident microglia population. J Neuroinflammation. 2012;9:228.PubMedPubMedCentralCrossRef
241.
Rahimzadeh A, Mirakabad FS, Movassaghpour A, Shamsasenjan K, Kariminekoo S, Talebi M, et al. Biotechnological and biomedical applications of mesenchymal stem cells as a therapeutic system. Artif Cells Nanomed Biotechnol. 2016;44(2):559–70.PubMedCrossRef
242.
Brenneman M, Sharma S, Harting M, Strong R, Cox CS Jr, Aronowski J, et al. Autologous bone marrow mononuclear cells enhance recovery after acute ischemic stroke in young and middle-aged rats. J Cereb Blood Flow Metab. 2010;30(1):140–9.PubMedCrossRef
243.
Liu N, Chen R, Du H, Wang J, Zhang Y, Wen J. Expression of IL-10 and TNF-alpha in rats with cerebral infarction after transplantation with mesenchymal stem cells. Cell Mol Immunol. 2009;6(3):207–13.PubMedPubMedCentralCrossRef
244.
Mora-Lee S, Sirerol-Piquer MS, Gutiérrez-Pérez M, Gomez-Pinedo U, Roobrouck VD, López T, et al. Therapeutic effects of hMAPC and hMSC transplantation after stroke in mice. PLoS One. 2012;7(8):e43683.PubMedPubMedCentralCrossRef
245.
Mays R, Borlongan C, Yasuhara T, Hara K, Maki M, Carroll J, et al. Development of an allogeneic adherent stem cell therapy for treatment of ischemic stroke. J Exp Stroke Transl Med. 2010;3:34–46.CrossRef
246.
Yang B, Hamilton JA, Valenzuela KS, Bogaerts A, Xi X, Aronowski J, et al. Multipotent adult progenitor cells enhance recovery after stroke by modulating the immune response from the spleen. Stem Cells. 2017;35(5):1290–302.PubMedCrossRef
247.
Plessers J, Dekimpe E, Van Woensel M, Roobrouck VD, Bullens DM, Pinxteren J, et al. Clinical-grade human multipotent adult progenitor cells block CD8+ cytotoxic T lymphocytes. Stem Cells Transl Med. 2016;5(12):1607–19.PubMedPubMedCentralCrossRef
248.
Mays R, Deans R. Adult adherent cell therapy for ischemic stroke: clinical results and development experience using MultiStem. Transfusion. 2016;56(4):6S–8S.PubMedCrossRef
249.
Osanai T, Houkin K, Uchiyama S, Minematsu K, Taguchi A, Terasaka S. Treatment evaluation of acute stroke for using in regenerative cell elements (TREASURE) trial: rationale and design. Int J Stroke. 2018;13(4):444–8.PubMedCrossRef
250.
Mays RW, Savitz SI. Intravenous cellular therapies for acute ischemic stroke. Stroke. 2018;49(5):1058–65.PubMedCrossRef
Metadata
Title
The spleen may be an important target of stem cell therapy for stroke
Authors
Zhe Wang
Da He
Ya-Yue Zeng
Li Zhu
Chao Yang
Yong-Juan Lu
Jie-Qiong Huang
Xiao-Yan Cheng
Xiang-Hong Huang
Xiao-Jun Tan
Publication date
01-12-2019
Publisher
BioMed Central
Keyword
Stroke
Published in
Journal of Neuroinflammation / Issue 1/2019
Electronic ISSN: 1742-2094
DOI
https://doi.org/10.1186/s12974-019-1400-0

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