目的将神经干细胞(NSCs)移植和神经生长因子(NGF)单独及联合应用于大脑中动脉阻塞(MCAo)模型大鼠,观察NGF和NSCs移植对大鼠缺血性脑卒中神经功能恢复的作用及NGF对自体和移植NSCs的影响。方法体外分离、培养新生大鼠海马NSCs,BrdU标记。实验动物随机分为A组(MCAo组)、B组(MCAo+NGF组)、C组(MCAo+NSCs组)及D组(MCAo+NGF+NSCs组),每组16只,移植后进行神经功能损害评分(NSS),用免疫组化行BrdU、槽蛋白检测,分析结果。结果移植后的2周、4周神经功能评分显示D组显著好于其他3组(P〈0.05).B组与C组显著好于A组(P〈0.05)。B组的槽蛋白及BrdU阳性细胞数显著多于A组(P〈0.05),D组的BrdU阳性细胞数显著多于C组(P〈0.05)。结论NSCs移植和NGF单独及联合应用对MCAo大鼠的神经功能恢复均有作用,二者联合具有协同作用。NGF对自体NSCs的激活、增殖有促进作用,对移植NSCs的增殖有促进作用。
Objective To observe the effect of neural stem cell (NSC) transplantation and nerve growth factor (NGF) on neurological function recovery in rats with ischemic stroke induced by transient middle cerebral artery occlusion (MCAO). Methods Cultured hippocampal NSCs isolated from neonate rats were labeled with 13rdU. Sixty-four rats subjected to transient MCAO were randomized equally into 4 groups, namely group A (MCAO model group), group B (model group with NGF treatment, group C (model group with NSC transplantation), and group D (model group with both NGF and NSC transplantation). The neurological deficits of the rats were evaluated with neurological severity score (NSS) after the treatment, and the brain tissues were examined with immunohistochemical and immunofluorescent staining for BrdU and nestin expression. Results The NSS of rats in group D 2 and 4 weeks after transplantation was significantly lower than that in the other 3 groups (P〈0.05), and the scores in groups B and C were significantly lower than those in group A (P〈0.05). The number of BrdU- and nestin-positive cells was significantly greater in group B than in group A (P〈0.05), and BrdU-positive cells were markedly more numerous in group D than in group C (P〈0.05). Conclusion Both NSC transplantation and NGF treatment can obviously improve the neurological function of rats after MCAO, but their combined use shows stronger effects. NGF can promote autologous NSC activation and proliferation, with also stimulatory effect on the proliferation of transplanted NSCs.