Sims N R, Pulsinelli W A
Department of Neurology, Cornell University Medical College, White Plains, New York.
J Neurochem. 1987 Nov;49(5):1367-74. doi: 10.1111/j.1471-4159.1987.tb01001.x.
Mitochondrial respiratory function, assessed from the rate of oxygen uptake by homogenates of rat brain subregions, was examined after 30 min of forebrain ischemia and at recirculation periods of up to 48 h. Ischemia-sensitive regions which develop extensive neuronal loss during the recirculation period (dorsal-lateral striatum, CA1 hippocampus) were compared with ischemia-resistant areas (paramedian neocortex, CA3 plus CA4 hippocampus). All areas showed reductions (to 53-69% of control) during ischemia for oxygen uptake rates determined in the presence of ADP or an uncoupling agent, which then recovered within 1 h of cerebral recirculation. In the ischemia-resistant regions, oxygen uptake rates remained similar to control values for at least 48 h of recirculation. After 3 h of recirculation, a significant decrease in respiratory activity (measured in the presence of ADP or uncoupling agent) was observed in the dorsal-lateral striatum which progressed to reductions of greater than 65% of the initial activity by 24 h. In the CA1 hippocampus, oxygen uptake rates were unchanged for 24 h, but were significantly reduced (by 30% in the presence of uncoupling agent) at 48 h. These alterations parallel the development of histological evidence of ischemic cell change determined previously and apparently precede the appearance of differential changes between sensitive and resistant regions in the content of high-energy phosphate compounds. These results suggest that alterations of mitochondrial activity are a relatively early change in the development of ischemic cell death and provide a sensitive biochemical marker for this process.
在前脑缺血30分钟后以及长达48小时的再灌注期，通过大鼠脑亚区域匀浆的氧摄取率评估线粒体呼吸功能。将在再灌注期发生广泛神经元损失的缺血敏感区域（背外侧纹状体、海马CA1区）与缺血耐受区域（正中旁新皮层、海马CA3加CA4区）进行比较。在存在ADP或解偶联剂的情况下测定的缺血期间，所有区域的氧摄取率均降低（降至对照值的53 - 69%），然后在脑再灌注1小时内恢复。在缺血耐受区域，氧摄取率在至少48小时的再灌注期内保持与对照值相似。再灌注3小时后，在背外侧纹状体观察到呼吸活性显著降低（在存在ADP或解偶联剂的情况下测定），到24小时时进展至初始活性降低超过65%。在海马CA1区，氧摄取率在24小时内无变化，但在48小时时显著降低（在存在解偶联剂的情况下降低30%）。这些改变与先前确定的缺血性细胞变化的组织学证据的发展情况平行，并且显然先于敏感区域和耐受区域之间高能磷酸化合物含量差异变化的出现。这些结果表明，线粒体活性改变是缺血性细胞死亡发展过程中相对较早的变化，并为该过程提供了一个敏感的生化标志物。
