Yatsushige Hiroshi, Yamaguchi Mitsuo, Zhou Changman, Calvert John W, Zhang John H
Department of Physiology, Loma Linda University School of Medicine, Loma Linda, CA, USA.
Stroke. 2005 Jul;36(7):1538-43. doi: 10.1161/01.STR.0000170713.22011.c8. Epub 2005 Jun 9.
Inflammation could play a role in cerebral vasospasm after subarachnoid hemorrhage (SAH). SP600125 a c-Jun N-terminal kinase (JNK) inhibitor reduces inflammation. The present study examined if SP600125 could reduce cerebral vasospasm.
Twenty-seven dogs were assigned to 5 groups: control, SAH, SAH plus dimethyl sulfoxide (DMSO), SAH plus SP600125 (10 micromol/L), and SAH plus SP600125 (30 micromol/L). SAH was induced by the injection of autologous blood into the cisterna magna on day 0 and day 2. Angiograms were evaluated on day 0 and day 7. The behavior of the dogs was evaluated daily. The activation of the JNK pathway, the infiltration of leukocytes, and the production of cytokines were also evaluated.
Severe vasospasm was observed in the basilar artery of SAH and DMSO dogs. The JNK signaling pathway was activated in the basilar artery after SAH and SP600125 reduced angiographic and morphological vasospasm and improved behavior scores with a concomitant reduction of infiltrated leukocytes and IL-6 production.
These results demonstrate that SP600125 attenuated cerebral vasospasm through a suppressed inflammatory response, which may provide a novel therapeutic target for cerebral vasospasm.
炎症可能在蛛网膜下腔出血（SAH）后的脑血管痉挛中起作用。SP600125是一种c-Jun氨基末端激酶（JNK）抑制剂，可减轻炎症。本研究探讨SP600125是否能减轻脑血管痉挛。
将27只犬分为5组：对照组、SAH组、SAH加二甲基亚砜（DMSO）组、SAH加SP600125（10微摩尔/升）组和SAH加SP600125（30微摩尔/升）组。在第0天和第2天通过向枕大池注射自体血诱导SAH。在第0天和第7天评估血管造影。每天评估犬的行为。还评估JNK途径的激活、白细胞浸润和细胞因子的产生。
在SAH组和DMSO组犬的基底动脉中观察到严重血管痉挛。SAH后基底动脉中JNK信号通路被激活，SP600125减少了血管造影和形态学上的血管痉挛，并改善了行为评分，同时减少了浸润的白细胞和IL-6的产生。
这些结果表明，SP600125通过抑制炎症反应减轻了脑血管痉挛，这可能为脑血管痉挛提供一种新的治疗靶点。
