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

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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.