MK-801内源性激活脑缺血后成年大鼠海马神经干细胞

Investigation of Internal Activating Neural Stem Cell by NMDA Receptor Antagonist Administration Following Focal Ischemic Insults

目的:研究兴奋性氨基酸(NMDA)受体拮抗剂MK801对脑缺血后海马区神经干细胞(NSCs)激活的作用。方法:将40只SD大鼠分成对照组和实验组,两组大鼠均采用传统线栓法作成大脑中动脉缺血再灌注模型,实验组大鼠腹腔注射MK801,对照组腹腔注射生理盐水,通过免疫组织化学技术标记鼠脑海马齿状回颗粒细胞层(SGZ)、室管膜下层(SVZ)注射后第3,7,11,18d的Brdu、Nestin阳性细胞数。结果:对照组大鼠Brdu、Nestin阳性细胞7d在SGZ出现一小高峰,然后迅速下降,11d阳性细胞甚少;而实验组Brdu、Nestin阳性细胞3d在SVZ明显表达,7～11d在SGZ区达高峰,并可持续至18d,两组比较,有统计学意义(P<0.01)。结论:NMDA受体拮抗剂MK801在脑缺血后,能促进大鼠海马区NSCs的增殖、分化。

Objective: To investigate the effect of NMDA receptor antagonist MK-801 on NSC proliferation and neural stem cell(NSC) differentiation in the adult rat SGZ, SVZ and cortex in focal ischemic insults produced by middle cerebral artery occlusion (MCAO). Methods: Forty SD rats were assigned into two groups as the experiment group (Ⅰ) and control group (Ⅱ). All rats were subjected to MACO for two hours. Rats in GroupⅠwere injected intraperitoneally with the NMDA receptor antagonist MK-801 and rats in GroupⅡwere injected intraperitoneally with saline. The rate of Brdu positive cells and Nestin postive cells were compared in SGZ, SVZ and infract contex. Results: In Group Ⅱ, Brdu positive cells and Nestin positive cells increased in SVZ 3 days after reperfusion, reached a slight peak after 7 and 11 days in SGZ, decreased after 11 days and scarcely detected after 18 days. But in Gorup Ⅰ after treated by MK-801, Brdu positive cells and Nestin postive cells significantly increased than in group Ⅱ after 3, 7, and 11 days in SVZ and SGZ. The proliferation was found in high level before the 18th day. Especially, Brdu and Nestin positive cells were significantly expressed near the infract contex. Conclusion: NMDA receptor antagonist treatment serves as a valuable tool to activate NSC proliferation and differentiation in cerebrum after infraction.