Clausen T, Zauner A, Levasseur J E, Rice A C, Bullock R
Division of Neurosurgery, Medical College of Virginia, Virginia Commonwealth University, P.O. Box 980631, 23298-0631, Richmond, VA, USA.
Brain Res. 2001 Jul 20;908(1):35-48. doi: 10.1016/s0006-8993(01)02566-5.
Recently, evidence has become available implicating mitochondrial failure as a crucial factor in the pathogenesis of acute brain damage following severe traumatic brain injury (TBI). However, it remains unclear how mitochondrial dysfunction affects cerebral metabolism. Therefore the aim of the study was to evaluate the impact of 'isolated' mitochondrial failure on local cerebral metabolism.
Cerebral mitochondrial metabolism was blocked by local microdialysis perfusion with cyanide in seven cats. Local brain tissue oxygen tension (p(tiO(2))), carbon dioxide tension (p(tiCO(2))) and pH, as well as extracellular cerebral fluid, glucose, lactate, pyruvate and glutamate were monitored, using a Neurotrend sensor and microdialysis, respectively. Tissue oxygen consumption was measured in a microrespirometric system, and ultrastructural changes evaluated via electron microscopy.
Brain tissue oxygen tension increased from a baseline of 31+/-9 mmHg to 84+/-30 mmHg after 60 min of cyanide perfusion (P<0.05), concomitant a decrease in oxygen consumption from 14.45+/-3.91 microl/h/mg to 10.83+/-1.74 microl/h/mg (P<0.05). Brain tissue pH was decreased after 60 min of cyanide perfusion (6.83+/-0.16) compared to baseline (7.07+/-0.39) (P<0.05), whereas p(tiCO(2)) did not show significant changes. Lactate massively increased from a baseline of 599+/-270 micromol/l to 2609+/-1188 micromol/l immediately after cyanide perfusion (P<0.05). The lactate:glucose ratio increased from 0.79+/-0.15 before cyanide perfusion to 6.40+/-1.44 at 40 min after cyanide perfusion (P<0.05), while no significant changes in the lactate:pyruvate ratio could be observed. Glutamate increased from a baseline of 11.6+/-7.2 micromol/l to 61.4+/-44.7 micromol/l after cyanide perfusion (P<0.05).
The results of this study show that 'isolated' cerebral mitochondrial failure initiates changes in cerebral substrates and biochemistry, which are very similar to most of the changes seen after severe human head injury, except for the early fall in p(tiO(2)), further indicating a crucial involvement of mitochondrial impairment in the development of brain damage after TBI.
最近，有证据表明线粒体功能衰竭是重度创伤性脑损伤（TBI）后急性脑损伤发病机制中的关键因素。然而，线粒体功能障碍如何影响脑代谢仍不清楚。因此，本研究的目的是评估“孤立性”线粒体功能衰竭对局部脑代谢的影响。
通过对7只猫进行局部微透析灌注氰化物来阻断脑线粒体代谢。分别使用Neurotrend传感器和微透析监测局部脑组织氧分压（p(tiO(2))）、二氧化碳分压（p(tiCO(2))）和pH值，以及细胞外脑脊液、葡萄糖、乳酸、丙酮酸和谷氨酸。在微量呼吸测定系统中测量组织氧消耗，并通过电子显微镜评估超微结构变化。
氰化物灌注60分钟后，脑组织氧分压从基线的31±9 mmHg升高至84±30 mmHg（P<0.05），同时氧消耗从14.45±3.91微升/小时/毫克降至10.83±1.74微升/小时/毫克（P<0.05）。氰化物灌注60分钟后，脑组织pH值（6.83±0.16）较基线（7.07±0.39）降低（P<0.05），而p(tiCO(2))无显著变化。氰化物灌注后，乳酸立即从基线的599±270微摩尔/升大幅增加至2609±1188微摩尔/升（P<0.05）。乳酸与葡萄糖的比值从氰化物灌注前的0.79±0.15增加至灌注后40分钟的6.40±1.44（P<0.05），而乳酸与丙酮酸的比值无显著变化。氰化物灌注后，谷氨酸从基线的11.6±7.2微摩尔/升增加至61.4±44.7微摩尔/升（P<0.05）。
本研究结果表明，“孤立性”脑线粒体功能衰竭引发脑底物和生物化学变化，这与严重人类头部损伤后所见的大多数变化非常相似，但早期p(tiO(2))下降除外，进一步表明线粒体损伤在TBI后脑损伤发展中起关键作用。
