Glial Cell Therapy Using Neuroprotective effects of Glia

大脑中动脉闭塞(MCAO)及再灌流可导致大鼠行为功能障碍，大脑皮层和纹状体大量神经元丢失。将外源性小胶质细胞移植到侧脑室。在大脑中动脉闭塞期间，局灶性脑缺血所致的行为功能障碍受到明显抑制。当时，许多小胶质细胞迁移到缺血灶中，几乎检测不到小胶质细胞来源的神经元样细胞。为了探讨帕金森病的移植策略，我们评估了纹状体(ST)和黑质(SN)或纹状体(ST)和丘脑底核(STN)的双重移植是否能诱导6-羟基多巴胺损伤大鼠的功能恢复。将小鼠ES细胞来源的神经元移植到ST，但不能单独移植到STN或SN，显著减少了甲基苯丙胺引起的旋转。二次移植在恢复旋转行为方面也是有效的。在偏侧帕金森病大鼠的同侧纹状体，酪氨酸羟化酶(TH)免疫反应几乎完全消失，但在ST、STN和SN的移植细胞和发芽纤维中检测到TH免疫反应。这些结果表明，ST的参与和作为移植地点以及ES细胞来源的神经元的数量都是影响偏侧帕金森病行为疗效的重要因素。

Middle cerebral artery occlusion (MCAo) and reperfusion caused behavioral dysfunction with massive neuronal loss in the rat cerebral cortex and striatum. When exogenous microglia were transplanted into the i.c.v. during MCA occlusion, focal ischemia-induced behavioral dysfunction was significantly inhibited. At that time, many microglia migrated into the ischemic lesion, and microglia-derived neuron-like cells were barely detectable. These results suggest that exogenous microglia protect against focal ischemia-induced neurodegeneration and improve behavioral dysfunction.To investigate a transplantation strategy for Parkinson's disease, we assessed whether double-transplants in the striatum (ST) and substantia nigra (SN), or ST and subthalamic nucleus (STN) induce functional recovery in 6-hydroxydopamine-lesioned rats. Methamphetamine-induced rotation was significantly reduced by transplantation of mouse ES cell-derived neurons into the ST, but not the STN or SN alone. Double-transplantation was also effective at recovering rotational behavior. Although immunoreactivity for tyrosine hydroxylase (TH) was almost completely lost in the ipsilateral striatum in hemiparkinsonian rats, TH immunoreactivity was detected in transplanted cells and sprouting fibers in the ST, STN and SN. These results suggest that both the involvement of ST and as a place of transplantation and the number of ES cell-derived neurons are essential factors for efficacy on hemiparkinsonian behaviors.