大鼠脑缺血耐受与脑自体神经干细胞的增殖

Ischemic tolerance in the brain and proliferation of autologous neural stem cells in rats

背景:脑缺血耐受与脑自体神经干细胞均具有脑保护作用,但前者能否促使脑自体神经干细胞增殖,学者们报道不一致。目的:明确缺血预处理与大鼠脑梗死后7d海马区自体神经干细胞增殖的关系,以及其对大鼠脑梗死后神经行为学评分的影响。方法:采用二次线栓法建立局灶-局灶性SD大鼠脑缺血耐受模型,40只SD雄性大鼠随机分为:假手术组,缺血组,假手术+缺血组,预缺血+缺血组,每组10只。脑梗死后3,7d采用Zea-Longa评分方法进行神经行为学评分,运用荧光免疫组织化学技术检测大鼠脑缺血侧海马区BrdU标记阳性细胞数量。结果与结论:脑梗死后3,7d的Zea-Longa神经行为学评分,预缺血+缺血组低于缺血组、假手术+缺血组(P<0.01),而缺血组和假手术+缺血组间差异无显著性意义(P>0.05)。脑梗死后7d缺血侧海马区BrdU标记阳性细胞数,缺血组、假手术+缺血组、预缺血+缺血组高于假手术组(P<0.01);预缺血+缺血组高于缺血组、假手术+缺血组(P<0.01);而缺血组和假手术+缺血组间差异无显著性意义(P>0.05)。结果表明缺血预处理可促进大鼠脑梗死后海马区齿状回颗粒下层成体神经干细胞的增殖,并能改善其神经功能缺损症状。

BACKGROUND：Brain ischemic tolerance and autologous neural stem cells have protective effects on the brain,but whether the former can contribute to the proliferation of autologous neural stem cells remains unclear.OBJECTIVE：To explore the relationship between ischemic preconditioning in brain and proliferation of endogenous neural stem cells in the hippocampus at 7 days following cerebral infarction,and to observe influence of ischemic preconditioning on the status of rats＇ neurological deficit after cerebral infarction.METHODS：The focal-focal ischemic tolerance models of Sprague Dawley rats were established using the twice suture method.A total of 40 male Sprague Dawley rats were randomly divided into sham surgery group,ischemia group,sham surgery ＋ ischemia group and ischemic preconditioning ＋ ischemia group,with 10 rats in each group.The neurological status was assessed using Zea-Longa neurological deficit scores at 3 and 7 days following cerebral infarction.Fluorescent immunohistochemistry was utilized to determine the number of BrdU-positive cells in the hippocampus of the ischemic side of rats.RESULTS AND CONCLUSION：Zea-Longa neurological deficit scores were lower in the ischemic preconditioning ＋ ischemia group compared with ischemia group and sham surgery ＋ ischemia group at 3 and 7 days following cerebral infarction（P〈0.01）.There was no significant difference between ischemia group and sham surgery ＋ ischemia group（P 0.05）.At 7 days following cerebral infarction,the number of BrdU-positive cells in the hippocampus of ischemic side was greater in the ischemia group,sham surgery ＋ ischemia group and ischemic preconditioning ＋ ischemia group compared with sham surgery group（P〈0.01）;the number was greater in the ischemic preconditioning ＋ ischemia group compared with ischemia group and sham surgery＋ ischemia group（P〈0.01）.No significant difference was determined between ischemia group and sham surgery ＋ ischemia group（P〉0.05）.Results suggest that ischemic preconditioning could facilitate the proliferation of endogenous neural stem cells in hippocampus dentate gyrus infragranular layer after ischemic cerebral infarction in rats,and improve the status of rats＇ neurological deficits.