胚胎神经干细胞移植对大鼠脑创伤后认知功能障碍的影响

Influence of embryonic neural stem cell transplantation on cognitive dysfunction following traumatic brain injury in rats

目的探讨脑创伤后胚胎神经干细胞移植对大鼠认知功能障碍的影响。方法成年雄性SD大鼠80只,随机平均分成4组:对照组、脑创伤组、脑创伤神经干细胞移植组和脑创伤PBS移植组。应用免疫组织化学方法观察伤后移植细胞在体内的分布和迁移,同时检测海马局部脑组织中神经生长因子(NGF)、脑源性神经生长因子(BDNF)的表达;采用Morris水迷宫实验评价大鼠伤后的空间学习记忆能力。结果神经干细胞移植后7、14、21和28d,移植区可检测到BrdU标记的阳性细胞。移植后7、14d时神经干细胞移植组伤后海马及周边局部脑组织中NGF的光密度(IOD)值分别为0.495 4±0.013 4、0.576 7±0.021 1,BDNF的IOD值分别为0.474 5±0.042 5、0.556 3±0.032 1,较其他组增高(P<0.05);神经干细胞移植组各时间点搜索安全岛逃避潜伏期较脑创伤组和PBS移植组有改善(P<0.05)。结论胚胎神经干细胞移植后海马局部脑组织中神经营养因子表达发生改变,对伤后认知功能障碍的恢复有着重要作用。

Objective To explore the influence of embryonic neural stem cell （ENSC） transplantation on learning and memory dysfunction after traumatic brain injury in rats. Methods A total of 80 adult male SD rats were randomly divided into control group, traumatic brain injury （TBI） group, traumatic brain injury and neural stem cell transplantation （TBI＋NSC） group, traumatic brain injury and PBS transplantation （TBI ＋ PBS）group. Immunohistochemistry was used to detect the distribution and migration of BrdU＋ and the changes of nerve growth factor （NGF） and brain derived neurophic factor （BDNF） expression in the hippocampus following traumatic brain injury. The spatial cognitive functions of animals were examined by Morris water maze. Results ENSCs marked with BrdU were found in the hippocampus at 7, 14, 21, and 28 d after transplantation. Increased expression of NGF and BDNF proteins was found around the hippocampus in the TBI＋ NSC group, with the IOD values at day 7 being 0. 495 4±0. 013 4 for NGF and 0. 474 5±0. 042 5 for BDNF, and the values at day 14 being 0. 576 7±0. 021 1 for NGF and 0. 556 3±70. 032 1 for BDNF, which were significantly higher than those in other groups （P〈 0.05）. The escape latency of TBI＋ NSC group was significantly decreased compared with TBI and TBI＋ PBS groups （P〈 0.05）. Conclusion Neurophic factors are changed in the hippocampus following transplantation of ENSCs, which is of great importance for the recovery of cognitive dysfunction following traumatic brain injury.