Inflammation and Stroke: An Overview

Overview

Journal Neurotherapeutics

Specialty Neurology

Date 2016 Oct 13

PMID 27730544

Citations 426

Authors

Josef Anrather

Costantino Iadecola

Affiliations

Soon will be listed here.

Abstract

The immune response to acute cerebral ischemia is a major factor in stroke pathobiology and outcome. While the immune response starts locally in occluded and hypoperfused vessels and the ischemic brain parenchyma, inflammatory mediators generated in situ propagate through the organism as a whole. This "spillover" leads to a systemic inflammatory response first, followed by immunosuppression aimed at dampening the potentially harmful proinflammatory milieu. In this overview we will outline the inflammatory cascade from its starting point in the vasculature of the ischemic brain to the systemic immune response elicited by brain ischemia. Potential immunomodulatory therapeutic approaches, including preconditioning and immune cell therapy will also be discussed.

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References

Stevens S, Ciesielski T, Marsh B, Yang T, Homen D, Boule J . Toll-like receptor 9: a new target of ischemic preconditioning in the brain. J Cereb Blood Flow Metab. 2008; 28(5):1040-7. PMC: 3037270. DOI: 10.1038/sj.jcbfm.9600606. View

Rosell A, Cuadrado E, Ortega-Aznar A, Hernandez-Guillamon M, Lo E, Montaner J . MMP-9-positive neutrophil infiltration is associated to blood-brain barrier breakdown and basal lamina type IV collagen degradation during hemorrhagic transformation after human ischemic stroke. Stroke. 2008; 39(4):1121-6. DOI: 10.1161/STROKEAHA.107.500868. View

Kaito M, Araya S, Gondo Y, Fujita M, Minato N, Nakanishi M . Relevance of distinct monocyte subsets to clinical course of ischemic stroke patients. PLoS One. 2013; 8(8):e69409. PMC: 3732285. DOI: 10.1371/journal.pone.0069409. View

Garcia-Bonilla L, Iadecola C . Peroxiredoxin sets the brain on fire after stroke. Nat Med. 2012; 18(6):858-9. PMC: 3955950. DOI: 10.1038/nm.2797. View

Seifert H, Hall A, Chapman C, Collier L, Willing A, Pennypacker K . A transient decrease in spleen size following stroke corresponds to splenocyte release into systemic circulation. J Neuroimmune Pharmacol. 2012; 7(4):1017-24. PMC: 3518577. DOI: 10.1007/s11481-012-9406-8. View

Vendrame M, Gemma C, Pennypacker K, Bickford P, Sanberg C, Sanberg P . Cord blood rescues stroke-induced changes in splenocyte phenotype and function. Exp Neurol. 2006; 199(1):191-200. DOI: 10.1016/j.expneurol.2006.03.017. View

Abete P, Testa G, Cacciatore F, Della-Morte D, Galizia G, Langellotto A . Ischemic preconditioning in the younger and aged heart. Aging Dis. 2012; 2(2):138-48. PMC: 3295052. View

Garcia-Bonilla L, Moore J, Racchumi G, Zhou P, Butler J, Iadecola C . Inducible nitric oxide synthase in neutrophils and endothelium contributes to ischemic brain injury in mice. J Immunol. 2014; 193(5):2531-7. PMC: 4147670. DOI: 10.4049/jimmunol.1400918. View

Eising G, Mao L, Schmid-Schonbein G, Engler R, Ross J . Effects of induced tolerance to bacterial lipopolysaccharide on myocardial infarct size in rats. Cardiovasc Res. 1996; 31(1):73-81. View

10.

Gottfried-Blackmore A, Kaunzner U, Idoyaga J, Felger J, McEwen B, Bulloch K . Acute in vivo exposure to interferon-gamma enables resident brain dendritic cells to become effective antigen presenting cells. Proc Natl Acad Sci U S A. 2009; 106(49):20918-23. PMC: 2791588. DOI: 10.1073/pnas.0911509106. View

11.

Cervera A, Planas A, Justicia C, Urra X, Jensenius J, Torres F . Genetically-defined deficiency of mannose-binding lectin is associated with protection after experimental stroke in mice and outcome in human stroke. PLoS One. 2010; 5(2):e8433. PMC: 2815773. DOI: 10.1371/journal.pone.0008433. View

12.

Offner H, Vandenbark A, Hurn P . Effect of experimental stroke on peripheral immunity: CNS ischemia induces profound immunosuppression. Neuroscience. 2008; 158(3):1098-111. PMC: 2666964. DOI: 10.1016/j.neuroscience.2008.05.033. View

13.

Vahidy F, Rahbar M, Zhu H, Rowan P, Bambhroliya A, Savitz S . Systematic Review and Meta-Analysis of Bone Marrow-Derived Mononuclear Cells in Animal Models of Ischemic Stroke. Stroke. 2016; 47(6):1632-9. PMC: 4879076. DOI: 10.1161/STROKEAHA.116.012701. View

14.

Ludewig P, Sedlacik J, Gelderblom M, Bernreuther C, Korkusuz Y, Wagener C . Carcinoembryonic antigen-related cell adhesion molecule 1 inhibits MMP-9-mediated blood-brain-barrier breakdown in a mouse model for ischemic stroke. Circ Res. 2013; 113(8):1013-22. DOI: 10.1161/CIRCRESAHA.113.301207. View

15.

Rezaie A . Protease-activated receptor signalling by coagulation proteases in endothelial cells. Thromb Haemost. 2014; 112(5):876-82. PMC: 4218909. DOI: 10.1160/TH14-02-0167. View

16.

Moskowitz M, Lo E, Iadecola C . The science of stroke: mechanisms in search of treatments. Neuron. 2010; 67(2):181-98. PMC: 2957363. DOI: 10.1016/j.neuron.2010.07.002. View

17.

Benakis C, Brea D, Caballero S, Faraco G, Moore J, Murphy M . Commensal microbiota affects ischemic stroke outcome by regulating intestinal γδ T cells. Nat Med. 2016; 22(5):516-23. PMC: 4860105. DOI: 10.1038/nm.4068. View

18.

Planas A, Chamorro A . Regulatory T cells protect the brain after stroke. Nat Med. 2009; 15(2):138-9. DOI: 10.1038/nm0209-138. View

19.

Emerich D, Dean 3rd R, Bartus R . The role of leukocytes following cerebral ischemia: pathogenic variable or bystander reaction to emerging infarct?. Exp Neurol. 2002; 173(1):168-81. DOI: 10.1006/exnr.2001.7835. View

20.

Del Zoppo G, Schmid-Schonbein G, Mori E, Copeland B, Chang C . Polymorphonuclear leukocytes occlude capillaries following middle cerebral artery occlusion and reperfusion in baboons. Stroke. 1991; 22(10):1276-83. DOI: 10.1161/01.str.22.10.1276. View