Mechanism for the Development of Irreversible Damages in Cerebral Ischemia.

为阐明缺血性不可逆损伤的病理生理机制，我们采用高效液相色谱法、近红外光谱光度法和磁共振成像技术分析了沙鼠脑缺血模型的生化和生理参数的序列变化，并与免疫组织化学变化进行了比较。我们建立了同时评估10至50微克干重脑组织区域能量代谢物水平变化和免疫组织化学变化的方法。区域ATP水平的降低似乎是免疫组化损伤发生的先决条件。2 .磁共振弥散加权成像显示组织水扩散系数迅速降低，提示离子泵失效，能量衰竭导致细胞骨架和细胞损伤。近红外光谱分析结果表明，细胞色素氧化酶的完全还原似乎先于ATP.4的降低。微管蛋白与MAPIA的易损性比较表明，在缺血中，微管蛋白的损伤与不可逆损伤的关系似乎比MAPIA更密切。在延迟性神经元死亡区域检测到n -乙酰天冬氨酸水平的区域性下降，提示神经元丢失和脑内不可逆损伤的敏感标志。在培养的星形胶质细胞缺氧/再氧化模型中，观察到与沙鼠脑缺血模型相似的能量状态紊乱和应激蛋白的诱导。后脑与前脑缺血一样，存在选择性缺血易感性。从这些结果来看，脑缺血的不可逆损伤可能是细胞色素氧化酶完全减少、ATP耗竭、离子泵失效和细胞骨架蛋白降解的结果。

To elucidate the pathophysiological mechanism for ischemic irreversible damage, we analyzed the sequential changes of biochemical and physiological parameters by use of HPLC,near infra-red spectro-photometry and magnetic resonance imaging, and compared them with the immunohistochemical changes in the gerbil model of cerebral ischemia.1. We established the method for the simultaneous assessment of changes in regional levels of energy metabolites and immunohistochemical changes in brain tissues of 10 to 50 microgram dry weight. The decrease of regional ATP level seemed prerequisite for the development of immunohistochemical damages.2. The diffusion-weighted magnetic resonance imaging showed prompt decrease of diffusion coefficient of tissue water, indicating ion pump failure as the results of energy failure caused cytoskeletal and cell damage.3. The results by near-infrared spectroscopy indicated complete reduction of cytochrome oxidase seemed preceded for the decrease of ATP.4. The comparison of vulnerability between tubulin and MAPIA indicated damages of tubulin seemed more closely related to irreversible damage than those of MAPIA in ischemia.5. The regional decrease in N-acetyl aspartate levels was detected in the area of delayd neuronal death, indicating the sensitive marker for the neuronal loss and irreversible damages in the brain.6. In hypoxia/reoxygenation model using cultured astrocytes, similar derangement of energy states and induction of stress proteins were observed as in the gerbil model of cerebral ischemia.7. In hindbrain regions, selective vulnerability to the ischemia existed as in the case of forebrain ischemia. From these results, irreversible damages in cerebral ischemia could be the result of complete reduction of cytochrome oxidase, ATP depletion, ion pump failure, and degradation of cytoskeletal proteins.