Isolation and functional analysis of genes related to delayed neuronal death in mouse hippocampus

我们用基因诱捕法分离了小鼠海马CA1区表达的一些未知基因。在小鼠短暂性脑缺血模型（即双侧颈总动脉结扎）中分析了这些基因的功能。利用蛋白转导的方法将基因产物诱导入脑，确定其在缺血中的功能。在未来，更多与神经元损伤和保护相关的未知基因将被分离出来。在缺血性脑损伤的治疗方面，我们对临床已经使用的药物进行了研究。然后我们报道了丹曲林和异丙酚可以减少海马CA1亚区缺血后延迟性神经元死亡，这种神经保护作用不仅是由于细胞外谷氨酸的减少，而且还具有抗氧化作用。此外，人尿源性胰蛋白酶抑制剂乌司他丁脑室内大量灌注可减少大鼠大脑中动脉闭塞局灶性缺血模型的梗死体积。我们将研究各种药物如自由基清除剂和麻醉剂的神经保护作用。神经干细胞作为脑室下区室管膜细胞，在缺血性脑损伤中的作用已引起广泛关注。我们在大鼠大脑中动脉闭塞模型中证实了局灶性脑缺血时室管膜细胞的迁移、增殖和分化。关于这个有趣的现象，我们正在研究基因的参与。

We have isolated some unknown genes expressed in the mouse hippocampal CA1 region using a gene trapping method. The function of these genes has been analyzed in the mouse transient cerebral ischemic model, i.e., ligation of bilateral common carotid arteries. Moreover, the gene products are going to be induced into the brain with the use of protein transduction method to determine the functions in ischemia. In the future, more unknown genes related to neuronal injury and protection will be isolated. With regard to treatment of post-ischemic brain injury, we investigated the drugs already used in clinical practice. Then we reported that dantrolene and propofol could reduce the post-ischemic delayed neuronal death in the hippocampal CA1 sub field, and that the neuroprotection is caused by not only the decrease of extracellular glutamate but also antioxidative effects. Furthermore, massive intracerebroventricular ulinastatin, a human urine-derived trypsin inhibitor, could reduce the infarct volume in the rat focal ischemic model of middle cerebral artery occlusion. We are going to study the neuro-protective effects of various agents such as free radical scavengers and anesthetics. Great attention has been paid to the action of neural stem cells, ependymal cells in the subventricular zone, in ischemic brain damage. We demonstarted that ependymal cells migrate, proliferate, and differentiate in response to focal cerebral ischemia in rat model of middle cerebral artery occlusion. In relation to this interesting phenomenon, we are investigating the participation of genes.