Gil Chan H, Kim Yu R, Lee Hong J, Jung Da H, Shin Hwa K, Choi Byung T
Department of Korean Medical Science, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam 50612, Republic of Korea.
Graduate Training Program of Korean Medicine for Healthy Aging, School of Korean Medicine, Pusan National University, Yangsan, Gyeongsangnam 50612, Republic of Korea.
Exp Ther Med. 2018 Jan;15(1):745-750. doi: 10.3892/etm.2017.5443. Epub 2017 Nov 6.
Previous studies have demonstrated that aripiprazole (APZ), a third-generation atypical antipsychotic drug, exhibits anti-depressant and neuroprotective effects by promoting dopaminergic neuronal cell recovery in stroke. To investigate the neuroprotective effects of APZ, behavioral and histopathological experiments were performed in the current study a mouse model of middle cerebral artery occlusion (MCAO)-induced ischemia following administration of APZ. The subacute phase of ischemic assaults was divided into 3 periods, each with a duration of 5 days, according to the start of APZ (3 mg/kg) administration (1-5, 5-9 or 10-14 days following MCAO). The beneficial effects of APZ on motor behavior demonstrated in the cylinder, rotarod and wire suspension tests were greatest when APZ was administered 1-5 days following MCAO, with clear improvements in motor function compared with vehicle-treated mice. Histopathological analysis revealed that prominent atrophic changes occurred in the striatum of MCAO mice and that these changes were reduced following APZ treatment. APZ also attenuated dopaminergic neuronal injury in the striatum. Cell death and microglial activation were decreased and the expression of Ca/calmodulin-dependent protein kinase II δ was enhanced following APZ treatment. These results indicate that the atypical antipsychotic drug, APZ, exhibits a neuroprotective effect in dopaminergic neuronal cells that may improve behavioral function following ischemic stroke.
先前的研究表明，阿立哌唑（APZ）作为第三代非典型抗精神病药物，通过促进中风中多巴胺能神经元细胞的恢复，表现出抗抑郁和神经保护作用。为了研究APZ的神经保护作用，在本研究中，对给予APZ后的大脑中动脉闭塞（MCAO）诱导的缺血小鼠模型进行了行为和组织病理学实验。根据APZ（3mg/kg）给药开始时间（MCAO后1-5天、5-9天或10-14天），将缺血攻击的亚急性期分为3个阶段，每个阶段持续5天。当在MCAO后1-5天给予APZ时，在圆筒试验、转棒试验和悬线试验中显示出的APZ对运动行为的有益作用最大，与给予赋形剂处理的小鼠相比，运动功能有明显改善。组织病理学分析显示，MCAO小鼠纹状体出现明显萎缩性变化，而APZ治疗后这些变化减少。APZ还减轻了纹状体中多巴胺能神经元的损伤。APZ治疗后细胞死亡和小胶质细胞活化减少，钙/钙调蛋白依赖性蛋白激酶IIδ的表达增强。这些结果表明，非典型抗精神病药物APZ在多巴胺能神经元细胞中表现出神经保护作用，这可能改善缺血性中风后的行为功能。
