Department of Anesthesiology, University of Maryland School of Medicine, Baltimore, MD 21201, USA.
J Neurotrauma. 2013 Mar 1;30(5):367-81. doi: 10.1089/neu.2012.2339.
Mitochondrial dysfunction may be central to the pathophysiology of traumatic brain injury (TBI) and often can be recognized cytologically by changes in mitochondrial ultrastructure. This study is the first to broadly characterize and quantify mitochondrial morphologic alterations in surgically resected human TBI tissues from three contiguous cortical injury zones. These zones were designated as injury center (Near), periphery (Far), and Penumbra. Tissues from 22 patients with TBI with varying degrees of damage and time intervals from TBI to surgical tissue collection within the first week post-injury were rapidly fixed in the surgical suite and processed for electron microscopy. A large number of mitochondrial structural patterns were identified and divided into four survival categories: normal, normal reactive, reactive degenerating, and end-stage degenerating profiles. A tissue sample acquired at 38 hours post-injury was selected for detailed mitochondrial quantification, because it best exhibited the wide variation in cellular and mitochondrial changes consistently noted in all the other cases. The distribution of mitochondrial morphologic phenotypes varied significantly between the three injury zones and when compared with control cortical tissue obtained from an epilepsy lobectomy. This study is unique in its comparative quantification of the mitochondrial ultrastructural alterations at progressive distances from the center of injury in surviving TBI patients and in relation to control human cortex. These quantitative observations may be useful in guiding the translation of mitochondrial-based neuroprotective interventions to clinical implementation.
线粒体功能障碍可能是创伤性脑损伤 (TBI) 病理生理学的核心，通常可以通过线粒体超微结构的变化在细胞学上识别。这项研究首次广泛描述和定量分析了三个连续皮质损伤区手术切除的人类 TBI 组织中线粒体形态的改变。这些区域被指定为损伤中心 (Near)、损伤周边 (Far) 和半影区 (Penumbra)。收集了 22 名 TBI 患者的组织，这些患者的损伤程度不同，从 TBI 到损伤后第一周内手术采集组织的时间间隔也不同，这些组织在手术过程中迅速固定并进行电子显微镜处理。确定了大量的线粒体结构模式，并将其分为四个存活类别：正常、正常反应性、反应性退化和终末退化。选择损伤后 38 小时采集的组织样本进行详细的线粒体定量，因为它最好地展示了所有其他病例中一致观察到的细胞和线粒体变化的广泛变化。线粒体形态表型的分布在三个损伤区之间以及与从癫痫切除术中获得的对照皮质组织之间存在显著差异。这项研究的独特之处在于，它比较了存活 TBI 患者从损伤中心逐渐远离时的线粒体超微结构改变，并与对照人类皮质进行了比较。这些定量观察结果可能有助于指导基于线粒体的神经保护干预措施向临床实施的转化。
