TNF-alpha receptor antagonist, R-7050, improves neurological outcomes following intracerebral hemorrhage in mice

NEUROSCIENCE LETTERS

卷:542

Article

King, Melanie D.¹  Alleyne, Cargill H., Jr.¹  Dhandapani, Krishnan M.¹ 

[1] Georgia Regents Univ, Med Coll Georgia, Dept Neurosurg, Augusta, GA USA

关键词: Hemorrhage;    Stroke;    Edema;    Blood-brain barrier;    Inflammation;   

DOI  :  10.1016/j.neulet.2013.02.051

来源: Elsevier

【 摘 要 】

Intracerebral hemorrhage (ICH), the most common form of hemorrhagic stroke, exhibits the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, treatment options for ICH are lacking due in part to a lack of feasible therapeutic targets. Inflammatory activation is associated with neurological deficits in pre-clinical ICH models and with patient deterioration after clinical ICH. In the present study, we tested the hypothesis that R-7050, a novel cell permeable triazoloquinoxaline inhibitor of the tumor necrosis factor receptor (TNFR) complex, attenuates neurovascular injury after ICH in mice. Up to 2 h post-injury administration of R-7050 significantly reduced blood-brain barrier opening and attenuated edema development at 24 h post-ICH. Neurological outcomes were also improved over the first 3 days after injury. In contrast, R-7050 did not reduce hematoma volume, suggesting the beneficial effects of TNFR inhibition were downstream of clot formation/resolution. These data suggest a potential clinical utility for TNFR antagonists as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH. (C) 2013 Elsevier Ireland Ltd. All rights reserved.

【 授权许可】

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