Immunomodulatory therapeutic strategies in stroke

dc.contributor.authorMalone, Kyle
dc.contributor.authorAmu, Sylvie
dc.contributor.authorMoore, Anne C.
dc.contributor.authorWaeber, Christian
dc.contributor.funderIrish Research Councilen
dc.contributor.funderHealth Research Boarden
dc.contributor.funderMarie Curieen
dc.date.accessioned2019-11-20T05:12:18Z
dc.date.available2019-11-20T05:12:18Z
dc.date.issued2019-06-20
dc.description.abstractThe role of immunity in all stages of stroke is increasingly being recognised, from the pathogenesis of risk factors to tissue repair, leading to the investigation of a range of immunomodulatory therapies. In the acute phase of stroke, proposed therapies include drugs targeting pro-inflammatory cytokines, matrix metalloproteinases, and leukocyte infiltration, with a key objective to reduce initial brain cell toxicity. Systemically, the early stages of stroke are also characterised by stroke-induced immunosuppression, where downregulation of host defences predisposes patients to infection. Therefore, strategies to modulate innate immunity post-stroke have garnered greater attention. A complementary objective is to reduce longer term sequelae, by focusing on adaptive immunity. Following stroke onset, the integrity of the blood-brain barrier is compromised, exposing central nervous system (CNS) antigens to systemic adaptive immune recognition, potentially inducing autoimmunity. Some pre-clinical efforts have been made to tolerise the immune system to CNS antigens pre-stroke. Separately, immune cell populations which exhibit a regulatory phenotype (T and B regulatory cells) have been shown to ameliorate post-stroke inflammation and contribute to tissue repair. Cell-based therapies, established in oncology and transplantation, could become a strategy to treat the acute and chronic stages of stroke. Furthermore, a role for the gut microbiota in ischemic injury has received attention. Finally, the immune system may play a role in remote ischemic preconditioning-mediated neuroprotection against stroke. The development of stroke therapies involving organs distant to the infarct site, therefore, should not be overlooked. This review will discuss the immune mechanisms of various therapeutic strategies, surveying published data and discussing more theoretical mechanisms of action that have yet to be exploited.en
dc.description.sponsorshipGOIPG/2017/431; HRA-POR-2015-1236en
dc.description.statusPeer revieweden
dc.description.versionPublished Versionen
dc.format.mimetypeapplication/pdfen
dc.identifier.articleid630en
dc.identifier.citationMalone, K., Amu, S., Waeber, C. and Moore, A.C., 2019. Immunomodulatory Therapeutic Strategies in Stroke. Frontiers in Pharmacology, 10, (630). DOI:10.3389/fphar.2019.00630en
dc.identifier.doi10.3389/fphar.2019.00630en
dc.identifier.eissn1663-9812
dc.identifier.endpage21en
dc.identifier.journaltitleFrontiers in Pharmacologyen
dc.identifier.startpage1en
dc.identifier.urihttps://hdl.handle.net/10468/9111
dc.identifier.volume10en
dc.language.isoenen
dc.publisherFrontiers Mediaen
dc.relation.projectinfo:eu-repo/grantAgreement/EC/FP7::SP3::PEOPLE/631246/EU/Sphingosine kinase 2-mediated preconditioning in stroke/SPK AND STROKEen
dc.relation.urihttps://www.frontiersin.org/articles/10.3389/fphar.2019.00630
dc.rights© 2019 Malone, Amu, Moore and Waeberen
dc.rights.urihttps://creativecommons.org/licenses/by/4.0/en
dc.subjectStrokeen
dc.subjectImmunomodulationen
dc.subjectIschaemiaen
dc.subjectImmuneen
dc.subjectTherapyen
dc.subjectNeuroinflammationen
dc.titleImmunomodulatory therapeutic strategies in strokeen
dc.typeArticle (peer-reviewed)en
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