Sysoev Yuriy Igorevich, Uzuegbunam Bright Chukwunwike, Okovityi Sergey Vladimirovich
Department of Pharmacology and Clinical Pharmacology, Saint-Petersburg State Chemical-Pharmaceutical University, St. Petersburg, Russia.
Institute of Translational Biomedicine (ITBM), Saint-Peterburg State University, St. Petersburg, Russia.
J Exp Pharmacol. 2019 Jun 19;11:53-63. doi: 10.2147/JEP.S199464. eCollection 2019.
To prove that our novel ethanolamine derivative (FDES) can normalize overall movement and exploratory activity of rats with traumatic brain injury (TBI) owing to its peculiar properties. TBI was modeled using controlled cortical impact injury (CCI) model method. The resulting neurological deficit, efficacy of the novel agent and other reference agents used were assayed in tests which evaluated overall movements and exploratory behavior of the rats. Finally, scopolamine in equimolar dose was used to estimate the role of cholinergic system in the efficacy of our agent. The tests included: limb-placing, open field, elevated plus maze, cylinder, and beam walking tests. Intraperitoneal administration of FDES at a dose of 10 mg/kg led to improvement of fore- and hind-limb functions of rats with traumatic brain injury as was shown in "Limb placing", "Open field" "Cylinder" and "Beam walking" tests. The new agent had no effects on traumatized rats behavior in the "Elevated Plus Maze" test. Simultaneous co-administration of scopolamine with FDES reduced the beneficial effects of the latter in rats with trauma. The neuroprotective effects of new agent were manifested in the reduction of motor deficiencies, and exploratory activity in the CCI model rats. In comparison with choline alfoscerate and citicoline, FDES showed more beneficial effects as were observed in most of the tests, and did not negatively influence the traumatized rats psychologically. Notably, it is possible that the neuroprotective influence of the new agent is mediated by its actions on the cholinergic system.
为证明我们新型乙醇胺衍生物（FDES）因其独特性质可使创伤性脑损伤（TBI）大鼠的整体运动和探索活动恢复正常。采用控制性皮质撞击损伤（CCI）模型方法建立TBI模型。在评估大鼠整体运动和探索行为的测试中，检测由此产生的神经功能缺损、新型药物及其他参考药物的疗效。最后，使用等摩尔剂量的东莨菪碱来评估胆碱能系统在我们药物疗效中的作用。测试包括：肢体放置、旷场、高架十字迷宫、圆筒和横梁行走测试。腹腔注射剂量为10mg/kg的FDES可改善创伤性脑损伤大鼠的前肢和后肢功能，这在“肢体放置”、“旷场”、“圆筒”和“横梁行走”测试中得到了体现。在“高架十字迷宫”测试中，该新型药物对创伤大鼠的行为没有影响。东莨菪碱与FDES同时给药会降低后者对创伤大鼠的有益作用。新型药物的神经保护作用表现为减少CCI模型大鼠的运动缺陷和探索活动。与阿福胆碱和胞磷胆碱相比，在大多数测试中，FDES显示出更有益的效果，且对创伤大鼠没有心理上的负面影响。值得注意的是，新型药物的神经保护作用可能是通过其对胆碱能系统的作用介导的。
