Genrikhs Elizaveta E, Stelmashook Elena V, Voronkov Dmitriy N, Novikova Svetlana V, Alexandrova Olga P, Gulyaev Mikhail V, Isaev Nickolay K
Research Center of Neurology, Volokolamskoe shosse 80, 125367 Moscow, Russia.
Faculty of Fundamental Medicine, M.V. Lomonosov Moscow State University, 119991 Moscow, Russia.
Antioxidants (Basel). 2020 May 2;9(5):377. doi: 10.3390/antiox9050377.
After traumatic brain injury (TBI), an increase in dysfunction of the limbs contralateral to injury focus was observed. Using different behavioral tests, we found that a single intravenous injection of methylene blue (MB, 1 mg/kg) 30 min after the injury reduced the impairment of the motor functions of the limbs from 7 to 120 days after TBI. Administration of methylene blue 30 min after the injury and then monthly (six injections in total) was the most effective both in terms of preservation of limb function and duration of therapeutic action. This therapeutic effect was clearly manifested from the seventh day and continued until the end of the experiment-by the 180th day after TBI. MB is known to possess antioxidant properties; it has a protective effect against TBI by promoting autophagy and minimizing lesion volume in the first two weeks after TBI. Studies of the brains on the 180th day after TBI demonstrated that the monthly treatment of animals with MB statistically significantly prevented an increase in the density of microglial cells in the ipsilateral hemisphere and a decrease in the thickness of the corpus callosum in the contralateral hemisphere in comparison with untreated animals. However, on the 180th day after TBI, the magnetic resonance imaging scan of the animal brains did not show a significant reduction in the volume of the lesion in MB-treated animals. These findings are important for understanding the development of the long-term effects of TBI and expand the required therapeutic window for targeted neuroprotective interventions.
创伤性脑损伤（TBI）后，观察到损伤灶对侧肢体功能障碍增加。通过不同的行为测试，我们发现损伤后30分钟单次静脉注射亚甲蓝（MB，1毫克/千克）可减轻TBI后7至120天肢体运动功能的损伤。损伤后30分钟注射亚甲蓝，然后每月注射一次（共注射六次），在保留肢体功能和治疗作用持续时间方面最为有效。这种治疗效果从第七天开始明显显现，并持续到实验结束——TBI后第180天。已知MB具有抗氧化特性；它通过促进自噬和使TBI后前两周的损伤体积最小化，对TBI具有保护作用。对TBI后第180天的大脑研究表明，与未治疗的动物相比，每月用MB治疗动物可在统计学上显著防止同侧半球小胶质细胞密度增加和对侧半球胼胝体厚度减小。然而，在TBI后第180天，动物大脑的磁共振成像扫描未显示MB治疗组动物的损伤体积有显著减小。这些发现对于理解TBI长期影响的发展很重要，并扩大了靶向神经保护干预所需的治疗窗口。
