The Immune Response to Acute Focal Cerebral Ischemia and Associated Post-stroke Immunodepression: A Focused Review

Overview

Journal Aging Dis

Specialty Geriatrics

Date 2014 Oct 3

PMID 25276490

Citations 59

Authors

Bolanle M Famakin

Affiliations

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Abstract

It is currently well established that the immune system is activated in response to transient or focal cerebral ischemia. This acute immune activation occurs in response to damage, and injury, to components of the neurovascular unit and is mediated by the innate and adaptive arms of the immune response. The initial immune activation is rapid, occurs via the innate immune response and leads to inflammation. The inflammatory mediators produced during the innate immune response in turn lead to recruitment of inflammatory cells and the production of more inflammatory mediators that result in activation of the adaptive immune response. Under ideal conditions, this inflammation gives way to tissue repair and attempts at regeneration. However, for reasons that are just being understood, immunosuppression occurs following acute stroke leading to post-stroke immunodepression. This review focuses on the current state of knowledge regarding innate and adaptive immune activation in response to focal cerebral ischemia as well as the immunodepression that can occur following stroke. A better understanding of the intricate and complex events that take place following immune response activation, to acute cerebral ischemia, is imperative for the development of effective novel immunomodulatory therapies for the treatment of acute stroke.

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References

Barone F, Schmidt D, Hillegass L, Price W, White R, Feuerstein G . Reperfusion increases neutrophils and leukotriene B4 receptor binding in rat focal ischemia. Stroke. 1992; 23(9):1337-47; discussion 1347-8. DOI: 10.1161/01.str.23.9.1337. View

Kim J, Gautam S, Chopp M, Zaloga C, Jones M, Ward P . 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. DOI: 10.1016/0165-5728(94)00138-e. View

Connolly Jr E, Winfree C, Prestigiacomo C, Kim S, Choudhri T, Hoh B . Exacerbation of cerebral injury in mice that express the P-selectin gene: identification of P-selectin blockade as a new target for the treatment of stroke. Circ Res. 1997; 81(3):304-10. DOI: 10.1161/01.res.81.3.304. View

Arnaout M . Structure and function of the leukocyte adhesion molecules CD11/CD18. Blood. 1990; 75(5):1037-50. View

Ginis I, Schweizer U, Brenner M, Liu J, Azzam N, Spatz M . TNF-alpha pretreatment prevents subsequent activation of cultured brain cells with TNF-alpha and hypoxia via ceramide. Am J Physiol. 1999; 276(5):C1171-83. DOI: 10.1152/ajpcell.1999.276.5.C1171. View

Lindsberg P, Carpen O, Paetau A, Karjalainen-Lindsberg M, Kaste M . Endothelial ICAM-1 expression associated with inflammatory cell response in human ischemic stroke. Circulation. 1996; 94(5):939-45. DOI: 10.1161/01.cir.94.5.939. View

Perry V, OConnor V . C1q: the perfect complement for a synaptic feast?. Nat Rev Neurosci. 2008; 9(11):807-11. DOI: 10.1038/nrn2394. View

Kleindorfer D, Lindsell C, Brass L, Koroshetz W, Broderick J . National US estimates of recombinant tissue plasminogen activator use: ICD-9 codes substantially underestimate. Stroke. 2008; 39(3):924-8. DOI: 10.1161/STROKEAHA.107.490375. View

Ovbiagele B, Goldstein L, Higashida R, Howard V, Johnston S, Khavjou O . Forecasting the future of stroke in the United States: a policy statement from the American Heart Association and American Stroke Association. Stroke. 2013; 44(8):2361-75. DOI: 10.1161/STR.0b013e31829734f2. View

10.

Lassmann H, Schmied M, Vass K, Hickey W . Bone marrow derived elements and resident microglia in brain inflammation. Glia. 1993; 7(1):19-24. DOI: 10.1002/glia.440070106. View

11.

Dunne A, ONeill L . The interleukin-1 receptor/Toll-like receptor superfamily: signal transduction during inflammation and host defense. Sci STKE. 2003; 2003(171):re3. DOI: 10.1126/stke.2003.171.re3. View

12.

Fassbender K, Mossner R, Motsch L, Kischka U, Grau A, Hennerici M . Circulating selectin- and immunoglobulin-type adhesion molecules in acute ischemic stroke. Stroke. 1995; 26(8):1361-4. DOI: 10.1161/01.str.26.8.1361. View

13.

Yang G, Schielke G, Gong C, Mao Y, Ge H, Liu X . Expression of tumor necrosis factor-alpha and intercellular adhesion molecule-1 after focal cerebral ischemia in interleukin-1beta converting enzyme deficient mice. J Cereb Blood Flow Metab. 1999; 19(10):1109-17. DOI: 10.1097/00004647-199910000-00007. View

14.

Goussev A, Zhang Z, Anderson D, Chopp M . P-selectin antibody reduces hemorrhage and infarct volume resulting from MCA occlusion in the rat. J Neurol Sci. 1999; 161(1):16-22. DOI: 10.1016/s0022-510x(98)00262-7. View

15.

Schilling M, Strecker J, Schabitz W, Ringelstein E, Kiefer R . Effects of monocyte chemoattractant protein 1 on blood-borne cell recruitment after transient focal cerebral ischemia in mice. Neuroscience. 2009; 161(3):806-12. DOI: 10.1016/j.neuroscience.2009.04.025. View

16.

Jin R, Zhu X, Liu L, Nanda A, Granger D, Li G . Simvastatin attenuates stroke-induced splenic atrophy and lung susceptibility to spontaneous bacterial infection in mice. Stroke. 2013; 44(4):1135-43. PMC: 3609888. DOI: 10.1161/STROKEAHA.111.000633. View

17.

Jauch E, Lindsell C, Broderick J, Fagan S, Tilley B, Levine S . Association of serial biochemical markers with acute ischemic stroke: the National Institute of Neurological Disorders and Stroke recombinant tissue plasminogen activator Stroke Study. Stroke. 2006; 37(10):2508-13. DOI: 10.1161/01.STR.0000242290.01174.9e. View

18.

Schilling M, Besselmann M, Muller M, Strecker J, Ringelstein E, 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(2):290-7. DOI: 10.1016/j.expneurol.2005.08.004. View

19.

Yang Q, Li J, Lu F, Wen A, Xiang J, Zhang L . Upregulated expression of toll-like receptor 4 in monocytes correlates with severity of acute cerebral infarction. J Cereb Blood Flow Metab. 2008; 28(9):1588-96. DOI: 10.1038/jcbfm.2008.50. View

20.

Ley K, Kansas G . Selectins in T-cell recruitment to non-lymphoid tissues and sites of inflammation. Nat Rev Immunol. 2004; 4(5):325-35. DOI: 10.1038/nri1351. View