Open AccessInterferon‐β Modulates Inflammatory Response in Cerebral Ischemia
Author(s) -
Kuo PingChang,
Scofield Barbara A.,
Yu IChen,
Chang FenLei,
Ganea Doina,
Yen JuiHung
Publication year - 2016
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.115.002610
Subject(s) - medicine , ischemia , tissue plasminogen activator , inflammation , microglia , excitotoxicity , stroke (engine) , multiple sclerosis , brain ischemia , central nervous system , cytokine , pharmacology , immunology , glutamate receptor , receptor , mechanical engineering , engineering
Background Stroke is a leading cause of death in the world. In >80% of strokes, the initial acute phase of ischemic injury is due to the occlusion of a blood vessel resulting in severe focal hypoperfusion, excitotoxicity, and oxidative damage. Interferon‐β ( IFN β), a cytokine with immunomodulatory properties, was approved by the US Food and Drug Administration for the treatment of relapsing‐remitting multiple sclerosis for more than a decade. Its anti‐inflammatory properties and well‐characterized safety profile suggest that IFN β has therapeutic potential for the treatment of ischemic stroke. Methods and Results We investigated the therapeutic effect of IFN β in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFN β not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFN β modulates ischemic brain inflammation were identified. IFN β reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD 4 + T cells, and γδ T cells; inhibited the production of inflammatory mediators; suppressed the expression of adhesion molecules on brain endothelial cells; and repressed microglia activation in the ischemic brain. Conclusions Our results demonstrate that IFN β exerts a protective effect against ischemic stroke through its anti‐inflammatory properties and suggest that IFN β is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator.