Mechanism of the delayd neuronal death : a mitochondrial

短暂的全脑缺血导致啮齿动物和人类海马CA 1区锥体神经元再灌注后数天的细胞死亡。海马CA 1神经元死亡通常发生在初始缺血损伤后3-4天。这种延迟对于这种类型的细胞死亡的机制是必要的。然而，以前的假说并没有很好地解释延迟的原因和细胞死亡的确切机制。另一方面，线粒体（mt）基因表达的干扰可能是一种替代方法。部分由mtDNA编码的MT蛋白质的MT RNA水平和活性的降低仅发生在再灌注早期的CA 1神经元中，并且随着时间的推移而加重。相反，在CA 1细胞中，核DNA编码的mt酶的活性和mt DNA的水平保持完整，直到死亡。免疫组织化学染色显示，缺血后，参与线粒体在细胞体和外周之间穿梭运动的细胞质动力蛋白和驱动蛋白也出现早期和进行性减少，并且这种减少仅见于易损的CA 1区。并可能导致CA 1神经元的能量产生的进行性失败，最终导致细胞死亡。因此，线粒体假说可能为阐明海马CA 1区神经元迟发性死亡的机制提供一个新的、理想的假说。

Brief period of global brain ischemia causes cell death in hippocampal CA1 pyramidal neurons days after reperfusion in rodents and human. Hippocampal CA1 neuronal death usually occurs 3-4 days after an initial ischemic insult. Such delay is seeential for the mechanism of this type of cell death. However, previous hypotheses have not well explained the reason of the delay and the exact mechanism of the cell death. On the other hand, disturbance of mitochondrial (mt) gene expression could be an alternative. Reductions of a mt RNA level and the activity of a mt protein, encoded partly by mt DNA,occurred exclusively in the CA1 neurons at the early stage of reperfusion, and were aggravated in the course of time. In contrast, the activity of a nuclear DNA-encoded mt enzyme and the level of mt DNA remained intact in the CA1 cells until the death. Immunohistochemical stainings for cytoplasmic dynein and kinesin, that are involved in the shuttle movement of mitochondria between cell body and the periphery, also showed early and progressive decreases after ischemia, and the decreases were found exclusively in the vulnerable CA1 subfield.Disturbance of mt DNA expression may be due to dysfunction of the mt shuttle system, and could cause progressive failure of energy production of the CA1 neurons that eventually results in the cell death. Thus, mitochondrial hypothesis could provide a new and fantastic potential to elucidate the mechanism of the delayd neuronal death of hippocampal CA1 neurons.