Effects of Thrombin on Neurogenesis After Intracerebral Hemorrhage
Effects of Thrombin on Neurogenesis After Intracerebral Hemorrhage
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DOI：
10.1161/strokeaha.107.508911
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发表时间：
2008-07
期刊：
影响因子：
8.3
通讯作者：
Shuxu Yang;Shui-jiang Song;Y. Hua;Takehiro Nakamura;R. Keep;G. Xi
中科院分区：
文献类型：
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作者：
Shuxu Yang;Shui-jiang Song;Y. Hua;Takehiro Nakamura;R. Keep;G. Xi
背景和目的-脑出血（ICH）的神经发生尚未研究。凝血酶的形成可引起脑出血后急性脑损伤，但凝血酶也可刺激细胞增殖。本研究探讨了ICH是否发生神经发生以及凝血酶在ICH相关神经发生中的作用。方法本研究分为四个部分. (1)大鼠接受ICH或针刺（假手术）。处死大鼠进行双皮质素（DCX）蛋白质印迹分析和免疫组化。(2)大鼠脑出血或假手术后第7天和第9天腹腔注射5-溴-2 ′-脱氧尿苷（BrdU）。灌注脑以鉴定BrdU阳性细胞。(3)对大鼠进行尾状核内注射凝血酶（1U），并对脑进行取样用于蛋白质印迹。(4)大鼠在有或没有凝血酶抑制剂水蛭素的情况下发生ICH。对脑进行取样用于DCX定量。结果：脑出血后7天，同侧基底节区DCX水平开始升高，14天达高峰，1个月后逐渐下降。免疫组化结果显示，脑出血后2周，同侧脑室下区和基底节区DCX免疫反应增强。部分DCX阳性细胞为BrdU阳性。一个单位的凝血酶，这不会导致明显的脑损伤，被注射到尾状核。凝血酶增加同侧基底神经节DCX水平，水蛭素阻断ICH诱导的DCX上调。结论：我们的研究结果表明脑出血后神经发生，凝血酶可能在脑出血诱导的神经发生中起作用。
Background and Purposes— Neurogenesis in intracerebral hemorrhage (ICH) has not been investigated. Thrombin formation causes acute brain injury after ICH, but thrombin also can stimulate cell proliferation. The present study examined whether neurogenesis takes place in ICH and the role of thrombin in ICH-related neurogenesis. Methods— This study was divided into four parts. (1) Rats received either an ICH or a needle insertion (sham). The rats were killed for doublecortin (DCX) Western blot analysis and immunohistochemistry. (2) Rats had an ICH or a sham operation, and then received intraperitoneal injections of 5-bromo-2′-deoxyuridine (BrdU) at day-7 and day-9 later. Brains were perfused to identify BrdU-positive cells. (3) Rats had an intracaudate injection of thrombin (1 U) and brains were sampled for Western blots. (4) Rats had an ICH with or without a thrombin inhibitor, hirudin. The brains were sampled for DCX quantitation. Results— DCX levels in the ipsilateral basal ganglia started to increase as early as 7 days after ICH, peaked at 14 days, and then gradually decreased at 1 month. Immunohistochemistry also demonstrated that DCX immunoreactivity was increased in the ipsilateral subventricular zone and basal ganglia at 2 weeks after ICH. Some DCX-positive cells were BrdU-positive. One unit thrombin, which does not cause marked brain injury, was injected into the caudate. Thrombin increased DCX levels in the ipsilateral basal ganglia and hirudin blocked ICH-induced upregulation of DCX. Conclusions— Our results demonstrated that neurogenesis occurs in the brain after ICH and that thrombin may play a role in ICH-induced neurogenesis.