| First Author | Kuo PC | Year | 2016 |
| Journal | J Am Heart Assoc | Volume | 5 |
| Issue | 1 | PubMed ID | 26747000 |
| Mgi Jnum | J:350773 | Mgi Id | MGI:7664221 |
| Doi | 10.1161/JAHA.115.002610 | Citation | Kuo PC, et al. (2016) Interferon-beta Modulates Inflammatory Response in Cerebral Ischemia. J Am Heart Assoc 5(1) |
| abstractText | 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-beta (IFNbeta), 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 IFNbeta has therapeutic potential for the treatment of ischemic stroke. METHODS AND RESULTS: We investigated the therapeutic effect of IFNbeta in the mouse model of transient middle cerebral artery occlusion/reperfusion. We found that IFNbeta not only reduced infarct size in ischemic brains but also lessened neurological deficits in ischemic stroke animals. Further, multiple molecular mechanisms by which IFNbeta modulates ischemic brain inflammation were identified. IFNbeta reduced central nervous system infiltration of monocytes/macrophages, neutrophils, CD4(+) T cells, and gammadelta 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 IFNbeta exerts a protective effect against ischemic stroke through its anti-inflammatory properties and suggest that IFNbeta is a potential therapeutic agent, targeting the reperfusion damage subsequent to the treatment with tissue plasminogen activator. |
