实验性大脑皮质梗死后内源性神经干细胞活化与EphB2表达的关系

Relation between activation of endogenous neural stem cells and EphB2 expression after cerebral cortex infarction in hypertensive rats

目的探讨实验性大脑皮质梗死后内源性神经干细胞活化与EphB2表达的关系。方法将易卒中型肾血管性高血压大鼠的右侧大脑中动脉皮质支闭塞(MCAO),术后第1周和第4周处死取脑,用免疫组化和原位杂交检测不同时点大脑皮质及侧脑室下区EphB2及其mRNA、神经巢蛋白(nestin)和多聚唾液酸神经细胞黏附分子(PSANCAM)表达的变化。结果MCAO术后1周,梗死侧大脑皮质和侧脑室下区EphB2及其mRNA的阳性信号为12.9±4.0、23.1±4.6和12.1±4.4、27.0±3.4,低于对照组(17.2±3.8、28.4±2.1和17.2±2.7、31.8±2.8,均P<0.05),4周时与对照组差异无统计学意义(P>0.05);梗死侧侧脑室下区nestin阳性信号第1周为18.7±2.2,高于对照组(16.9±2.9,P<0.05),第4周时恢复正常;MCAO术后1周,梗死侧侧脑室下区PSANCAM阳性信号为17.7±2.2,高于对照组(14.5±2.2,P<0.05),可见PSANCAM阳性细胞沿胼胝体向梗死灶迁移,4周时其信号降低但仍高于对照组(P<0.05)。结论脑梗死能激活内源性神经干细胞增殖及迁移,脑梗死后内源性神经干细胞活化可能与EphB2表达下降有关。

Objective To investigate the relationship of EphB2 and proliferation and migration of endogenous neural stem cells after cerebral cortex infarction in hypertensive rats. Methods At the end of the Ist and the 4th week after distal ligation of right middle cerebral artery in stroke-prone renovascular hypertensive rats, the brains were sectioned for immunohistochemistry and in situ hybridization analysis as to determining the expression of EphB2 and its mRNA, nestin and PSA-NCAM in the cortex and subventricular zone（SVZ）. Results Ascomparedwiththecontrols（17.2±3.8,28.4±2.1;17.2±2.7,31.8±2.8）, EphB2 and its mRNA signals at ipsilateral cortex and SVZ （12. 9 ±4. 0, 23. 1 ±4.6;12. 1 ±4.4, 27.0 ± 3.4） were decreased at the end of the 1 st week after distal ligation of right middle cerebral artery （ P 〈 0. 05）, then returned to normal levels at the 4th week. Nestin signals at ipsilateral SVZ （ 18. 7 ±2. 2） were higher than that of the controls （ 16.9 ±2.9 ,P 〈0.05） at the end of the 1st week, then returned to normal levels at the 4th week. In the 1st week, PSA-NCAM signals （17.7 ± 2.2 ） were higher than those of the controls（ 14. 5 ± 2. 2,P 〈 0. 05 ）. PSA-NCAM positive cells migrated to infarct area along corpus c allosum. At the 4th week PSA-NCAM signals were decreased, but still elevated as compared with those in controls（ P 〈 0. 05 ）. Conclusions Results indicate that the proliferation and migration of endogenous neural stem cells at SVZ should be activated by cerebral cortex infarction and be related to the reduction of expression of EphB2.