Approach for the establishment of new way of brain resuscutation

脑缺血以延迟性神经细胞死亡的形式导致严重的损伤。我们从免疫抑制剂环孢素A(CsA)和FK506的作用机制方面探讨了迟发性神经细胞死亡的机制。我们发现CsA在前脑缺血中的强烈神经保护作用不仅是通过抑制促凋亡蛋白Bad的去磷酸化来抑制钙调神经诱导的细胞死亡，而且还通过亲环蛋白D(CyPD)保护线粒体通透性转换(MPT)孔的形成所致的线粒体膜损伤。这些结果为临床应用和开发治疗脑以及心脏和肝脏缺血性损伤的新药奠定了基础。

Brain ischemia leads to severe damage in the form of delayed neuronal cell death. We have been investigated the mechanisms of delayed neuronal cell death in terms of the mechanisms of immunosuppressant, such as cyclosporin A (CsA) and FK506. We show here the drastic neuroprotection of the CsA in the forebrain ischemia is not only due to inhibition of calcineurininduced cell death through dephosphorylation of proapoptotic protein Bad, but also due to protection of mitochonorial damage which is caused by the MPT (Mitochondrial Permeability Transition) pore formation through cyclophilin D (CyPD), one of the prolyl cis/trans isomerase family members.These results shed light on the clinical application and development of new drugs for the treatment of ischemic damage in the brain as well as in the heart and liver.