脑缺血再灌注神经干细胞原位激活的研究

目的 探讨大鼠局灶性脑缺血再灌注后不同时间、不同脑部位神经干细胞(NSC)原位激活的变化规律。方法 建立一侧大脑中动脉闭塞缺血再灌注模型,用5-溴脱氧尿苷(BrdU)标记脑内增殖细胞,免疫组化(SP法)技术检测大鼠缺血再灌注不同时间段缺血周边皮质、双侧侧脑室下区(SVZ)、海马齿状回下区(SGZ)具有增殖能力细胞BrdU表达变化。结果 对照组脑组织双侧SVZ、SGZ可见少量BrdU阳性标记细胞;单纯脑缺血2 h组脑组织BrdU阳性细胞数未见明显增加;再灌注3天组,缺血侧皮质、双侧SVZ和SGZBrdU阳性细胞明显增多(P<0.05),7天时达到高峰(P<0.001),11天时下降,且缺血侧与对侧相比,双侧SVZ呈对称分布,而SGZ以缺血侧增加为主(P<0.05)。结论 一侧大脑中动脉闭塞缺血再灌注可致成年大鼠脑内NSC原位激活,且NSC增殖于缺血后1周达到高峰,激活部位以双侧SVZ、缺血侧海马和周边皮质为主。

Activation of neural stem cells in situ following focal reversible ischemia in rat brain

Objective To sutdy changes in spatial and temporal expression of neural stem calls (NSCs) after focal ischemic middle cerebral occlusion/reperfusion in rat. Methods Thirty mature Wistar rats were randomly divided into five groups: sham-operated control group, simple ischemia group, 3-day(3 d), 7 d and 11 d reperfusion groups. After two hours of the right middle cerebral artery occlusion, the rats were reperfused for different time as mentioned above. During 24 h before each sampling, two doses of BrdU was intraperitoneally administered (8:30 AM and 4: 30 PM). In sham-operated control rats, the inserted thread was only 9 millimeter long. BrdU immunohistochemistry was applied to evaluate the activation of NSCs in cerebral cortex, SVZ and SGZ respectively. Results A few BrdU-positive cells were observed in the SVZ and SGZ in the control group. The number of BrdU-positive cells started to increase in 3 days after ischemia/reperfusion in the cerebral cortex, SVZ and SGZ and reached a peak in 7 days, then declined in 11 days. In addition, in contrast to SVZ in which the number of positive cells was equal, more cells in SC-Z were labeled in ischemia area than non-ischemia area. Conclusions Progenitor ceils of both SVZ and SGZ in iscbemia cortex, can be induced to proliferate by focal ischemia/reperfusion and the number of BrdU positive cells reached peak in first week following ischemia.