Regeneration of neuronal function by grafting neural stem cells

为了确定神经干细胞（NSCs）引入受损的中枢神经系统的可能的治疗潜力，我们研究了突触的形成和成人海马来源的NSCs的整合。首先，我们证明了成人NSCs可以分化为具有功能性突触传递和GABA能突触传递的神经元。这些结果支持这样的神经元可以整合到神经元回路中的概念（Exp. Neurol. 165：66-76，2000）。接下来，我们将这些NSC移植到具有短暂性全脑缺血的大鼠的海马中。短暂的四血管闭塞导致海马CA 1区锥体神经元损失90%至95%。在这个区域，1 - 3%的移植细胞存活;其中3 - 9%表达NeuN，一种神经元标记物。具有超过120个NeuN阳性细胞的大鼠在水迷宫测试中表现出受损的空间学习的部分改善。这些结果表明移植到缺血脑中的NSC能够分化成神经元并改善空间识别（Neurosci. Lett. 316：9-12，2001）。作为另一种神经元损伤模型，癫痫大鼠正在构建中。我们通过将子宫中的大鼠胎儿暴露于紫外线下来产生皮质发育不良的大鼠。这些大鼠也将接受NSC移植。

To determine the possible therapeutic potential of neural stem cells (NSCs) introduced into the damaged central nervous system, we examined a synapse formation and an integration of adult hippocampus-derived NSCs.First, we demonstrated that adult NSCs can differentiate into neurons with functional glutamatergic and GABAergic synaptic transmission in vitro. These results support the concept that such neurons could integrate into the neuronal circuitry (Exp. Neurol. 165 : 66-76, 2000).Next, we grafted these NSCs into the hippocampus of rats with transient global ischemia. Transient four-vessel occlusion yielded 90 to 95 % losses of pyramidal neurons in the hippocampal CA1 region. In this region, 1 to 3 % of the grafted cells survived ; and 3 to 9 % of them expressed NeuN, a neuronal marker. Rats with more than 120 NeuN-positive cells showed partial improvement of impaired spatial learning in a water maze test. These results suggest that NSCs grafted in the ischemic brain are able to differentiate into neurons and to improve spatial recognition (Neurosci. Lett. 316 : 9-12, 2001).As another model of neuronal damage, epileptic rats are under construction. We have produced rats with cortical dysplasia by exposing rat fetus in the uterus to UV light. These rats will also be subjected to transplantation of NSCs.