Research Center of Neurology, Volokolamskoe Shosse 80, 125367, Moscow, Russia.
M.V. Lomonosov Moscow State University, A.N. Belozersky Institute of Physico-Chemical Biology, 119991, Moscow, Russia.
Brain Res Bull. 2019 May;148:100-108. doi: 10.1016/j.brainresbull.2019.03.011. Epub 2019 Mar 29.
The protective effect of SkQR1, a mitochondria-targeted antioxidant, was investigated on the model of focal one-sided traumatic brain injury (TBI) of the sensorimotor cortex region from 1 to 7 days after the injury. TBI caused a reliable disruption of the functions of the limbs contralateral to injury focus. The intravenous single injection of SkQR1 (250 nmol/kg) but not C12R1 (a SkQR1 homologue devoid of the antioxidant group) 30 min after TBI reduced the impairment of the motor functions of the limbs. A statistically significant improvement in limb function in animals was shown using 3 different tests: limb-placing test, beam-walking test and grip strength test. A pronounced therapeutic effect appeared on the 1th day and lasted until the end of the experiment - the 7th day after TBI. Histopathological examination showed that in the group of animals that did not receive SkQR1 in the marginal layer of the lesion there was a marked increase in astroglial expression, infiltration with segmented neutrophils, and poor survivability of neurons compared with animals treated with SkQR1. The obtained results demonstrate that the single use of plastoquinone-containing mitochondria-targeted antioxidant SkQR1 at the early stages of development of traumatic brain damage can reduce TBI-related disruptions of limb functions, and that mechanisms of the brain damage after trauma are dependent on the production of mitochondrial reactive oxygen species.
SkQR1 是一种靶向线粒体的抗氧化剂，研究人员调查了它对体感皮质区局灶性单侧创伤性脑损伤（TBI）模型的保护作用，从损伤后 1 天到 7 天。TBI 可靠地破坏了损伤焦点对侧肢体的功能。TBI 后 30 分钟静脉注射 SkQR1（250nmol/kg）而不是 C12R1（一种缺乏抗氧化剂基团的 SkQR1 同源物）可减轻肢体运动功能的损伤。使用 3 种不同的测试，即肢体放置测试、平衡木行走测试和握力测试，显示动物的肢体功能有统计学意义的改善。在第 1 天出现明显的治疗效果，并持续到实验结束-损伤后第 7 天。组织病理学检查显示，与接受 SkQR1 治疗的动物相比，未接受 SkQR1 治疗的动物损伤边缘层的星形胶质细胞表达明显增加，分段中性粒细胞浸润，神经元存活率差。这些结果表明，在创伤性脑损伤发展的早期阶段，单一使用含有质体醌的靶向线粒体抗氧化剂 SkQR1 可以减轻 TBI 相关的肢体功能障碍，并且创伤后脑损伤的机制依赖于线粒体活性氧的产生。
