Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point.
Mitoquinone Helps Combat the Neurological, Cognitive, and Molecular Consequences of Open Head Traumatic Brain Injury at Chronic Time Point.
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米托醌有助于对抗慢性时间点开放性头部创伤性脑损伤的神经、认知和分子后果。
DOI：
10.3390/biomedicines10020250
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发表时间：
2022-01-24
期刊：
影响因子：
4.7
通讯作者：
Kobeissy F
中科院分区：
文献类型：
--
作者：
Haidar MA;Shakkour Z;Barsa C;Tabet M;Mekhjian S;Darwish H;Goli M;Shear D;Pandya JD;Mechref Y;El Khoury R;Wang K;Kobeissy F
创伤性脑损伤 (TBI) 在其起源、神经病理学和预后方面是一种异质性疾病，尚无 FDA 批准的治疗方法。 TBI的病理学复杂且尚未得到充分了解，这也是过去30年30多项临床试验III期失败的原因。 TBI 的多方面病理生理学涉及一系列代谢和分子事件，包括炎症、氧化应激、兴奋性毒性和线粒体功能障碍。在这项研究中，利用受控皮质冲击 (CCI) 诱导的开放式头部 TBI 小鼠模型，用于研究损伤后 30 天施用线粒体醌 (MitoQ) 的慢性保护作用。通过加西亚神经评分、爬杆、握力和粘合剂去除测试来评估神经功能，而通过物体识别、莫里斯水迷宫和强迫游泳测试来评估认知和行为功能。至于分子效应，通过免疫荧光染色来研究小胶质细胞增生、星形细胞增多、神经元细胞计数和轴突完整性。结果表明，MitoQ 在受伤后 30 天增强了神经功能和认知功能。 MitoQ 还减少了星形胶质细胞和小胶质细胞的活化，同时改善了皮质中的轴突完整性和神经元细胞计数。因此，我们得出结论，MitoQ 通过减少氧化应激、神经炎症和轴突损伤，在中度开头 CCI 小鼠模型中具有神经保护作用。
Traumatic brain injury (TBI) is a heterogeneous disease in its origin, neuropathology, and prognosis, with no FDA-approved treatments. The pathology of TBI is complicated and not sufficiently understood, which is the reason why more than 30 clinical trials in the past three decades turned out unsuccessful in phase III. The multifaceted pathophysiology of TBI involves a cascade of metabolic and molecular events including inflammation, oxidative stress, excitotoxicity, and mitochondrial dysfunction. In this study, an open head TBI mouse model, induced by controlled cortical impact (CCI), was used to investigate the chronic protective effects of mitoquinone (MitoQ) administration 30 days post-injury. Neurological functions were assessed with the Garcia neuroscore, pole climbing, grip strength, and adhesive removal tests, whereas cognitive and behavioral functions were assessed using the object recognition, Morris water maze, and forced swim tests. As for molecular effects, immunofluorescence staining was conducted to investigate microgliosis, astrocytosis, neuronal cell count, and axonal integrity. The results show that MitoQ enhanced neurological and cognitive functions 30 days post-injury. MitoQ also decreased the activation of astrocytes and microglia, which was accompanied by improved axonal integrity and neuronal cell count in the cortex. Therefore, we conclude that MitoQ has neuroprotective effects in a moderate open head CCI mouse model by decreasing oxidative stress, neuroinflammation, and axonal injury.
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作者：
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