Robertson Courtney L, Saraswati Manda, Fiskum Gary
Department of Pediatrics, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Neurochem. 2007 Jun;101(5):1248-57. doi: 10.1111/j.1471-4159.2007.04489.x. Epub 2007 Apr 2.
Mitochondria play central roles in acute brain injury; however, little is known about mitochondrial function following traumatic brain injury (TBI) to the immature brain. We hypothesized that TBI would cause mitochondrial dysfunction early (<4 h) after injury. Immature rats underwent controlled cortical impact (CCI) or sham injury to the left cortex, and mitochondria were isolated from both hemispheres at 1 and 4 h after TBI. Rates of phosphorylating (State 3) and resting (State 4) respiration were measured with and without bovine serum albumin. The respiratory control ratio was calculated (State 3/State 4). Rates of mitochondrial H(2)O(2) production, pyruvate dehydrogenase complex enzyme activity, and cytochrome c content were measured. Mitochondrial State 4 rates (ipsilateral/contralateral ratios) were higher after TBI at 1 h, which was reversed with bovine serum albumin. Four hours after TBI, pyruvate dehydrogenase complex activity and cytochrome c content (ipsilateral/contralateral ratios) were lower in TBI mitochondria. These data demonstrate abnormal mitochondrial function early (<or=4 h) after TBI in the developing brain. Future studies directed at reversing mitochondrial abnormalities could guide neuroprotective interventions after pediatric TBI.
线粒体在急性脑损伤中起核心作用；然而，对于未成熟脑创伤性脑损伤（TBI）后的线粒体功能却知之甚少。我们推测TBI会在损伤后早期（<4小时）导致线粒体功能障碍。未成熟大鼠左侧皮质接受控制性皮质撞击（CCI）或假手术损伤，在TBI后1小时和4小时从双侧半球分离线粒体。在有和没有牛血清白蛋白的情况下测量磷酸化（状态3）和静息（状态4）呼吸速率。计算呼吸控制率（状态3/状态4）。测量线粒体H(2)O(2)产生速率、丙酮酸脱氢酶复合体酶活性和细胞色素c含量。TBI后1小时，线粒体状态4速率（同侧/对侧比率）较高，牛血清白蛋白可使其逆转。TBI后4小时，TBI线粒体中的丙酮酸脱氢酶复合体活性和细胞色素c含量（同侧/对侧比率）较低。这些数据表明，发育中脑TBI后早期（≤4小时）线粒体功能异常。针对逆转线粒体异常的未来研究可能会为小儿TBI后的神经保护干预提供指导。
