Spinal Cord and Brain Injury Research Center, University of Kentucky, Lexington, KY, USA; Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
Department of Cell Systems and Anatomy, Neurology and Research Imaging Institute, University of Texas Health San Antonio, San Antonio, TX, USA.
Neurochem Int. 2017 Oct;109:117-125. doi: 10.1016/j.neuint.2017.04.004. Epub 2017 Apr 7.
Complex, multi-factorial secondary injury cascades are initiated following traumatic brain injury, which makes this a difficult disease to treat. The secondary injury cascades following the primary mechanical tissue damage, are likely where effective therapeutic interventions may be targeted. One promising therapeutic target following brain injury are mitochondria. Mitochondria are complex organelles found within the cell, which act as powerhouses within all cells by supplying ATP. These organelles are also necessary for calcium cycling, redox signaling and play a major role in the initiation of cell death pathways. When mitochondria become dysfunctional, there is a tendency for the cell to loose cellular homeostasis and can lead to eventual cell death. Targeting of mitochondrial dysfunction in various diseases has proven a successful approach, lending support to mitochondria as a pivotal player in TBI cell death and loss of behavioral function. Within this mixed mini review/research article there will be a general discussion of mitochondrial bioenergetics, followed by a brief discussion of traumatic brain injury and how mitochondria play an integral role in the neuropathological sequelae following an injury. We will also give an overview of one relatively new TBI therapeutic approach, Methylene Blue, currently being studied to ameliorate mitochondrial dysfunction following brain injury. We will also present novel experimental findings, that for the first time, characterize the ex vivo effect of Methylene Blue on mitochondrial function in synaptic and non-synaptic populations of mitochondria.
颅脑损伤后会引发复杂的多因素继发性损伤级联反应，这使得该病的治疗极具难度。继发性损伤级联反应继发于原发性机械性组织损伤，可能是有效治疗干预的目标所在。颅脑损伤后，一种有前途的治疗靶点是线粒体。线粒体是细胞内的复杂细胞器，通过提供 ATP 为所有细胞充当“能量工厂”。这些细胞器对于钙循环、氧化还原信号也很必要，并在启动细胞死亡途径方面发挥着主要作用。当线粒体功能失调时，细胞往往会失去细胞内稳态，并最终导致细胞死亡。针对各种疾病的线粒体功能障碍的靶向治疗已被证明是一种成功的方法，这为线粒体作为 TBI 细胞死亡和行为功能丧失的关键参与者提供了支持。在这篇混合的小型综述/研究文章中，将首先对线粒体生物能学进行一般性讨论，然后简要讨论颅脑损伤以及线粒体在损伤后的神经病理学后果中所起的重要作用。我们还将概述一种相对较新的 TBI 治疗方法亚甲蓝，目前正在研究该方法以改善颅脑损伤后的线粒体功能障碍。我们还将呈现新颖的实验发现，这是首次对亚甲蓝对突触和非突触线粒体线粒体功能的体外作用进行了特征描述。
