Anderson R E, Tan W K, Meyer F B
Thoralf M. Sundt Jr, MD Neurosurgical Research Laboratory, Mayo Clinic, Rochester, MN USA; Mayo Graduate School of Medicine, Rochester, MN USA.
J Stroke Cerebrovasc Dis. 1999 Nov-Dec;8(6):368-79. doi: 10.1016/s1052-3057(99)80044-5.
Within the ischemic penumbra, there is a heterogeneous development of cortical intracellular acidosis that is associated with selective neuronal injury. This experiment, which used a rabbit model of moderate focal cerebral ischemia, examined the time course for changes in intracellular brain pH, cortical blood flow, capillary bed density, and mitochondrial function in the ischemic penumbra. After cortical annotation of regions of intracellular acidosis in the ischemic penumbra, the animals underwent transcardiac carbon black perfusion for measurement of capillary bed density. Analysis of variance and Pearson's correlation coefficients were used to determine the relationship between capillary bed density, brain intracellular pH, mitochondrial function, and cortical blood flow. Thirty minutes after the onset of ischemia, cortical blood flow declined from 46+/-2 to 22+/-1 mL/100gm/min (P<.01) in all groups. The overall cortical intracellular brain pH measured 6.78+/-.01 compared with a preischemic value of 6.98+/-.01 (P<.05). Within this moderately ischemic cortex, there were small regions (1,000 to 45,000 mum(2)) of increased acidosis, meauring 6.68+/-.01, not associated with focal changes in cortical blood flow, occurring within 15 minutes of ischemia and persisting throughout the ischemic period. Capillary bed density progressively declined with ongoing ischemia occurring after the development of acidosis. For example, capillary bed density in preischemic controls was 338+/-6/mm(2), whereas after 1 hour of ischemia, it measured 147+/-12/mm(2), at 3 hours 97+/-23/mm(2), and at 6 hours 92+/-16/mm(2). Mitochondrial function was reduced coinciding with the decrease in capillary bed density. These data support the hypothesis that cortical acidosis in the ischemic penumbra facilitates the development of perfusion defects that subsequently lead to mitochondrial dysfunction.
在缺血半暗带内，皮质细胞内酸中毒呈异质性发展，这与选择性神经元损伤相关。本实验采用中度局灶性脑缺血兔模型，研究了缺血半暗带内细胞内脑pH值、皮质血流量、毛细血管床密度和线粒体功能的变化时间进程。在对缺血半暗带内细胞内酸中毒区域进行皮质标注后，对动物进行经心腔炭黑灌注以测量毛细血管床密度。采用方差分析和Pearson相关系数来确定毛细血管床密度、脑内细胞内pH值、线粒体功能和皮质血流量之间的关系。缺血发作30分钟后，所有组的皮质血流量从46±2降至22±1 mL/100gm/min（P<0.01）。总体皮质细胞内脑pH值为6.78±0.01，而缺血前值为6.98±0.01（P<0.05）。在这个中度缺血的皮质内，存在小区域（1000至45000μm²）酸中毒增加，pH值为6.68±0.01，与皮质血流量的局灶性变化无关，在缺血15分钟内出现并在整个缺血期持续存在。随着酸中毒发生后持续缺血，毛细血管床密度逐渐下降。例如，缺血前对照组的毛细血管床密度为338±6/mm²，而缺血1小时后为147±12/mm²，3小时时为97±23/mm²，6小时时为92±16/mm²。线粒体功能随着毛细血管床密度的降低而降低。这些数据支持以下假设：缺血半暗带内的皮质酸中毒促进灌注缺陷的发展，随后导致线粒体功能障碍。
