大鼠脑出血后内源性神经干细胞激活和增殖的实验研究

目的 观察大鼠脑出血模型内源性神经干细胞(NSCs)的激活、增殖情况及其对神经行为学表现的影响.方法 将72只SD大鼠按单双号分为脑出血组和假手术组.每组36只.脑出血组利用立体定向技术,将一定量的Ⅳ型胶原酶用微量进样器分别精确注入大鼠内囊诱导脑出血模型.假手术组注射等量体积的PBS.分别于术后1、7、14、21、28和35 d观察大鼠的神经功能表现.所有大鼠处死前1 d腹腔内注射5.溴脱氧尿嘧啶(BrdU),免疫组织化学方法动态检测大鼠脑内巢蛋白(nestin)和BrdU的表达.结果 假手术组大鼠脑内未见nestin和BrdU的表达.脑出血组血肿周围基底节和脑室下区可见nestin和BrdU的表达.脑出血后7 d后开始明显增加.14 d达高峰,21 d开始下降.28d恢复正常.脑出血后l～35d大鼠神经功能无明显恢复,与内源性NSCs的增殖程度无明显相关.结论 脑出血可导致内源性NSCs的激活和诱导其增殖:然而这种状态下NSCs的增殖能力和内源性NSCs对脑出血后神经功能缺损的修复均有限.

Neural stem cell activation and proliferation in situ after intracerebral hemorrhage:an experimental study in adult rats

Objective To observe neural stem cell activation and proliferation in situ afterintracerebal hemorrhage (ICH) and its effect on the neurological function of the injured adult rats.Methods Seventy-two adult rats were randomized into ICH and sham operation groups (n=36). In theICH group, type Ⅳ collagenase was injected into the internal capsule through a microinfusion pump toinduce intracerebral hemorrhage, and the rats in the sham operation group received only phosphate buffersolution injection. The neurological functions of the rats were observed by rotarod motor test on days 1, 7,14, 21, 28, and 35 after the injection. One day before sacrifice, the rots were subjected to intraperitonealBrdU injection to label the regenerated cells, and immunohistochemistry was used to detect theexpressions of nestin and BrdU in the brain tissue. Results No nestin- or BrdU-positive cells werefound in the brain of the rats in the sham operation group. In rats with ICH, nestin- and BrdU-positivecells were found predominantly in the basal ganglion around the hematoma, in the ependyma and near thesubventricular zone (SVZ) in the brain; the number of the positive cells increased significantly 7 daysafter ICH, peaked on day 14 and then significantly reduced on day 28. The rats exhibited no obviousimprovement of the impaired motor function over the period from day 1 to 35 after ICH. Activation andproliferation of the neural stem cells was not obviously related to the recovery of the neurologicalfunctions. Conclusion Endogeneous neural stem cells in the brain are activated in rats after ICH, butthese stem cells possess rather limited capacity of proliferation and can not sufficiently compensate forICH-induced neurological function impairment.