功能性电刺激对急性脑梗死大鼠运动功能及室管膜下区内源性神经干细胞的影响

The effects of functional electrical stimulation on motor function and on the proliferation, migration and differentiation of neural stem cells in the subventricular zone

目的观察不同时间点功能性电刺激（FES）对急性脑梗死大鼠神经功能和室管膜下区（SVZ）内源性神经干细胞增殖、迁移及分化的影响。方法采用大脑中动脉阻塞（MCAO）法制作急性腑梗死大鼠模型212只，其中128只大鼠符合入选标准，最终108只完成实验。将这108只大鼠按随机数字表法分为对照组、假刺激组和FES组，每组36只，每组再按治疗时间的不同分为治疗1、3、7和lgd四个亚组，每亚组9只大鼠。术后第3天开始以表面电极刺激瘫痪侧前肢，治疗强度（约4～5mA）以引起瘫痪侧出现伸腕伸指动作为准，每日1次，每次治疗15min。分别于治疗前和治疗各时间点，采用改良神经功能缺损评分（mNSS）法评定各组大鼠神经功能变化情况；采用免疫组织荧光化学法检测缺血侧脑组织SVZ的BrdU^＋／GFAP^＋、BrdU^＋／DCX^＋、BrdU^＋／NeuN^＋阳性细胞表达的动态改变。结果治疗第7天和第14天，FES组的mNSS评分与其余2组比较，差异有统计学意义（P〈0．05）；治疗第14天，单独行运动功能项目的评分比较，FES组的评分与其余2组比较，差异有统计学意义（P〈0．05）；FES组大鼠梗死侧SVZ的BrdU^＋细胞数目在FES治疗第7天达到高峰；FES组BrdU^＋／GFAP^＋阳性细胞数目表达在治疗第7天和第14天分别与假刺激组和对照组比较，差异均有统计学意义（P〈0．05）；BrdU^＋／DCX^＋细胞数目随着时间延长增加，在治疗第14天时FES组阳性细胞数日均高于假刺激组和对照组（P〈0．05）；BrdU^＋／NeuN^＋仅在治疗第14天时有少量表达，组间差异无统计学意义（P〉0．05）。结论FES治疗能够改善急性脑梗死大鼠神经功能，促进SVZ神经干细胞的增殖和分化。

Objective To investigate the effects of functional electrical stimulation （FES） on motor function and on the expression, proliferation, migration and differentiation of endogenous neural stem ceils in the subventricular zone （SVZ） after cerebral ischemia. Methods Middle cerebral artery occlusion （MCAO） was used to induce a model of cerebral ischemia in 108 rats using the modified Zea-Longa method of intraluminal filament occlusion. They were then randomly divided into an FES group, a placebo stimulation group and a control group with 36 cases in each. Superficial FES electrodes were pasted on the paralyzed forelimbs of the rats in the first two groups, though FES treat- ment was administered only to the FES group beginning on the 3rd day after the MCAO operation. The stimulation was designed to produce extension of the wrist and digits of the paralyzed forelimb. Before, and after 1, 3, 7 and 14 days of the treatment, the neurological deficit was evaluated using modified neurological severity scoring （mNSS）. BrdU^＋/ GFAP^＋, BrdU^＋/DCX^＋ and BrdU^＋/NeuN^＋ cells in the SVZ were detected using immunofluorescenee technique. Results After 7 and 14 days of treatment, the average motor function of the rats in the FES group had improved signif- icantly when compared with the averages of the other two groups. Compared with the other two groups, the average num- ber of BrdU^＋/GFAP^＋ positive cells in the isehemic SVZ was also significantly greater in the FES group after 7 and 14 days of treatment. After 14 days, BrdU^＋/Dex^＋ positive cells in the FES group had also increased significantly more,but only a few BrdU^＋/NeuN^＋ cells had appeared in any of the three groups. Conclusion FES can improve motor function after cerebral ischemia, and promote proliferation and differentiation of neural stem cells in the SVZ.