Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.
Necrostatin-1 reduces neurovascular injury after intracerebral hemorrhage.
复制标题
DOI：
10.1155/2014/495817
复制
发表时间：
2014
影响因子：
--
通讯作者：
Dhandapani KM
中科院分区：
文献类型：
--
作者：
King MD;Whitaker-Lea WA;Campbell JM;Alleyne CH Jr;Dhandapani KM
脑出血（ICH）是出血性中风最常见的形式，占所有中风的 15%。在所有卒中亚型中，ICH 的急性死亡率最高，长期预后最差。不幸的是，缺乏临床有效的治疗方案使得脑出血成为最难治疗的中风形式，这凸显了对新治疗靶点的需求。我们实验室最近的工作发现了坏死性凋亡抑制剂 necrostatin-1 在限制出血性损伤组织培养模型中神经血管损伤方面的新作用。在本研究中，我们测试了 necrostatin-1 可减少胶原酶诱导的小鼠脑出血后神经血管损伤的假设。与假受伤小鼠或给予非活性结构类似物 necrostatin-1 的小鼠相比，Necrostatin-1 在 ICH 后 72 小时显着减少血肿体积 54%。 Necrostatin-1 还可将细胞死亡限制为 48%，将血脑屏障开放减少 51%，将水肿发展减弱至假手术水平，并改善 ICH 后的神经行为结果。这些数据表明，necrostatin-1 和/或新型坏死性凋亡抑制剂作为辅助疗法具有潜在的临床效用，可减少脑出血后的神经损伤并改善患者的预后。
Intracerebral hemorrhage (ICH) is the most common form of hemorrhagic stroke, accounting for 15% of all strokes. ICH has the highest acute mortality and the worst long-term prognosis of all stroke subtypes. Unfortunately, the dearth of clinically effective treatment options makes ICH the least treatable form of stroke, emphasizing the need for novel therapeutic targets. Recent work by our laboratory identified a novel role for the necroptosis inhibitor, necrostatin-1, in limiting neurovascular injury in tissue culture models of hemorrhagic injury. In the present study, we tested the hypothesis that necrostatin-1 reduces neurovascular injury after collagenase-induced ICH in mice. Necrostatin-1 significantly reduced hematoma volume by 54% at 72 h after-ICH, as compared to either sham-injured mice or mice administered an inactive, structural analogue of necrostatin-1. Necrostatin-1 also limited cell death by 48%, reduced blood-brain barrier opening by 51%, attenuated edema development to sham levels, and improved neurobehavioral outcomes after ICH. These data suggest a potential clinical utility for necrostatin-1 and/or novel necroptosis inhibitors as an adjunct therapy to reduce neurological injury and improve patient outcomes after ICH.