Kogure K, Busto R, Schwartzman R J, Scheinberg P
Ann Neurol. 1980 Sep;8(3):278-90. doi: 10.1002/ana.410080310.
Temporal and site correlation of local cerebral blood flow (1-CBF), tissue redox state, energy metabolism, tissue pH, and cerebral electrophysiological activity in induced cerebral ischemia was performed in rats in an effort to obtain helpful clues for the management of occlusive cerebrovascular disease. CBF decreased acutely in both the embolized and nonembolized hemispheres but returned toward normal in 5 minutes. However, total cerebral oxidative metabolism remained depressed throughout the 30-minute observation period despite improved perfusion. The change in CBF correlated with the development and resolution of tissue acidosis, which was maximal 3 minutes after embolization but became alkaline after 30 minutes, possibly due to accumulation of sodium lactate. Oxidized form of nicotinamide-adenine dinucleotide and cytochrome a,a3 quickly became reduced in the ischemic core, but a tardyspontaneous postischemic tissue perfusion resulted in their hyperoxidation. The CBF-metabolism uncoupling as well as postischemic hyperoxidation of the electron transport system, which is associated with accumulation of pyruvate and lactate, probably resulted from stagnation of electron flow at the entrance to the mitochondrial respiratory processes. Seizures could not account for these results, as paroxysmal changes in the EEG usually appeared only in the nonembolized hemisphere and were not dependent upon lack of energy. These studies confirm that metabolic failure may persist in ischemic tissue despite adequate reperfusion, which may, in fact, contribute to tissue damage through hyperoxidation.
为了获得有助于治疗闭塞性脑血管疾病的线索,对大鼠诱导性脑缺血时的局部脑血流量(l-CBF)、组织氧化还原状态、能量代谢、组织pH值和脑电生理活动进行了时间和部位相关性研究。栓塞侧和未栓塞侧半球的脑血流量均急性下降,但在5分钟内恢复正常。然而,尽管灌注有所改善,但在整个30分钟的观察期内,全脑氧化代谢仍处于抑制状态。脑血流量的变化与组织酸中毒的发生和消退相关,组织酸中毒在栓塞后3分钟时最为严重,但在30分钟后变为碱性,这可能是由于乳酸钠的积累所致。烟酰胺腺嘌呤二核苷酸和细胞色素a,a3的氧化形式在缺血核心迅速还原,但缺血后组织灌注延迟导致它们过度氧化。脑血流量与代谢的解偶联以及电子传递系统的缺血后过度氧化,与丙酮酸和乳酸的积累有关,可能是由于线粒体呼吸过程入口处电子流停滞所致。癫痫不能解释这些结果,因为脑电图的阵发性变化通常仅出现在未栓塞侧半球,且不依赖于能量缺乏。这些研究证实,尽管再灌注充分,缺血组织中的代谢衰竭可能仍然存在,而这实际上可能通过过度氧化导致组织损伤。