Peer-Reviewed Journal Details
Mandatory Fields
Malone, K;Amu, S;Moore, AC;Waeber, C
2019
June
Frontiers In Pharmacology
Immunomodulatory Therapeutic Strategies in Stroke
Validated
Optional Fields
CEREBRAL-ARTERY OCCLUSION ACUTE ISCHEMIC-STROKE INTERLEUKIN-1 RECEPTOR ANTAGONIST REGULATORY T-CELLS MONOCYTE CHEMOATTRACTANT PROTEIN-1 PLASMINOGEN ACTIVATOR TREATMENT ADHESION MOLECULE-1 ANTIBODY IMMUNE MODULATOR FINGOLIMOD OXIDE SYNTHASE EXPRESSION NONHUMAN PRIMATE MODEL
10
The role of immunity in all stages of stroke is increasingly being recognized, 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 characterized 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 tolerize the immune system to CNS antigens pre-stroke. Separately, immune cell populations that exhibit a regulatory phenotype (T- and B-regulatory cells) have been shown to ameliorate poststroke 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 ischaemic injury has received attention. Finally, the immune system may play a role in remote ischaemic preconditioningmediated 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.
LAUSANNE
1663-9812
10.3389/fphar.2019.00630
Grant Details