Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part II: Suppression of astrocytic activation by a novel agent (R)-(-)-2-propyloctanoic acid (ONO-2506) leads to mitigation of delayed infarct expansion and early improvement of neurologic deficits
Astrocytic activation and delayed infarct expansion after permanent focal ischemia in rats. Part II: Suppression of astrocytic activation by a novel agent (R)-(-)-2-propyloctanoic acid (ONO-2506) leads to mitigation of delayed infarct expansion and early improvement of neurologic deficits
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DOI：
10.1097/00004647-200206000-00011
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发表时间：
2002-06-01
影响因子：
6.3
通讯作者：
Asano, T
中科院分区：
文献类型：
--
作者：
Tateishi, N;Mori, T;Asano, T
一种新的药物，（R）-（-）-2-丙基辛酸（ONO-2506），具有独特的性质，因为它调节活化的培养星形胶质细胞的功能，包括显着抑制S-100 β的合成。本研究探讨了是否管理这种代理将减轻延迟扩大梗死体积和神经功能缺损后，永久性大脑中动脉闭塞（pMCAO）大鼠。每日静脉内施用ONO-2506（10 mg/kg）消除了pMCAO后24至168小时之间的延迟性梗塞扩展，而急性梗塞扩展直到24小时不受影响。该药物显著降低活化星形胶质细胞中S-100 β和胶质细胞酸性蛋白的表达以及梗死周围区域中末端脱氧核苷酸转移酶介导的2 '-脱氧尿苷5'-三磷酸-生物素缺口末端标记阳性细胞的数量。早在ONO-2506初始给药后24小时，神经功能缺损就与赋形剂治疗组相比显著改善。该药物具有pMCAO后0至48小时的宽治疗时间窗。这些结果表明，由于ONO-2506诱导的星形胶质细胞活化的药理学调节，症状可以消退，而损伤的延迟扩展被阻止。星形胶质细胞活化的药理学调节可能赋予一种新的治疗中风的策略。
A novel agent, (R)-(-)-2-propyloctanoic acid (ONO-2506), has a unique property in that it modulates functions of activated cultured astrocytes, including pronounced inhibition of S-100beta synthesis. The present study examined whether administration of this agent would mitigate the delayed expansion of infarct volume and the neurologic deficits after permanent middle cerebral artery occlusion (pMCAO) in rats. Daily intravenous administration of ONO-2506 (10 mg/kg) abolished the delayed infarct expansion between 24 and 168 hours after pMCAO, whereas the acute infarct expansion until 24 hours was unaffected. The agent significantly reduced the expression of S-100beta and glial fibrillary acidic protein in the activated astrocytes and the number of terminal deoxynucleotidyl transferase-mediated 2'-deoxyuridine 5'-triphosphate-biotin nick end labeling-positive cells in the periinfarct area. The neurologic deficits were significantly improved, compared with the vehicle-treated groups, as early as 24 hours after the initial administration of ONO-2506. The agent had a wide therapeutic time window of 0 to 48 hours after pMCAO. These results indicate that because of the pharmacologic modulation of astrocytic activation induced by ONO-2506, symptoms can regress Whereas delayed expansion of the lesion is arrested. Pharmacologic modulation of astrocytic activation may confer a novel therapeutic strategy against stroke.