Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism
Ubiquinol treatment for TBI in male rats: Effects on mitochondrial integrity, injury severity, and neurometabolism
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DOI：
10.1002/jnr.24210
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发表时间：
2018-06-01
影响因子：
4.2
通讯作者：
Harris, Janna L.
中科院分区：
文献类型：
--
作者：
Pierce, Janet D.;Gupte, Raeesa;Harris, Janna L.
创伤性脑损伤（TBI）后，自由基增加和线粒体功能受损会对脑组织造成严重的继发性损伤。活性氧（ROS）的产生和细胞抗氧化防御的有效性之间的这种不平衡被称为氧化应激。通常没有足够的抗氧化剂来抑制ROS，导致大脑结构和功能的改变。通过给予抗氧化剂来减轻TBI后的氧化应激可能会减少继发性脑损伤，目前正在研究许多药物和补充剂。我们探索了一种名为泛醇（辅酶Q10的还原形式）的非处方补充剂，这是一种在大脑线粒体中天然产生的有效抗氧化剂。我们给大鼠动脉内注射泛醇，以确定它是否会减少线粒体损伤、细胞凋亡和挫伤性TBI的严重程度。将成年雄性F344大鼠随机分配到三个组中的一个：（1）盐水-TBI，（2）TBI前30分钟的泛醇（UB-PreTBI），或（3）TBI后30分钟的泛醇（UB-PostTBI）。我们发现，当泛醇在TBI之前或之后给药时，大鼠脑线粒体损伤、细胞凋亡和两种TBI严重程度的血清生物标志物胶质细胞酸性蛋白（GFAP）和泛素C末端水解酶-L1（UCH-L1）急性减少。然而，在体内神经代谢评估与质子磁共振波谱没有显示衰减损伤引起的变化。这些发现首次表明泛醇在TBI后保护线粒体并降低细胞损伤严重程度，并支持进一步研究泛醇作为TBI的有希望的辅助治疗。
Following traumatic brain injury (TBI), there is significant secondary damage to cerebral tissue from increased free radicals and impaired mitochondrial function. This imbalance between reactive oxygen species (ROS) production and the effectiveness of cellular antioxidant defenses is termed oxidative stress. Often there are insufficient antioxidants to scavenge ROS, leading to alterations in cerebral structure and function. Attenuating oxidative stress following a TBI by administering an antioxidant may decrease secondary brain injury, and currently many drugs and supplements are being investigated. We explored an over-the-counter supplement called ubiquinol (reduced form of coenzyme Q10), a potent antioxidant naturally produced in brain mitochondria. We administered intra-arterial ubiquinol to rats to determine if it would reduce mitochondrial damage, apoptosis, and severity of a contusive TBI. Adult male F344 rats were randomly assigned to one of three groups: (1) Saline-TBI, (2) ubiquinol 30 minutes before TBI (UB-PreTBI), or (3) ubiquinol 30 minutes after TBI (UB-PostTBI). We found when ubiquinol was administered before or after TBI, rats had an acute reduction in brain mitochondrial damage, apoptosis, and two serum biomarkers of TBI severity, glial fibrillary acidic protein (GFAP) and ubiquitin C-terminal hydrolase-L1 (UCH-L1). However, in vivo neurometabolic assessment with proton magnetic resonance spectroscopy did not show attenuated injury-induced changes. These findings are the first to show that ubiquinol preserves mitochondria and reduces cellular injury severity after TBI, and support further study of ubiquinol as a promising adjunct therapy for TBI.