Department of Medical Elementology and Toxicology, School of Chemical and Life Sciences, Jamia Hamdard, New Delhi 110062, India.
Division of Basic Medical Sciences, Indian Council of Medical Research, Ministry of Health and Family Welfare, Government of India, V. Ramalingaswamy Bhawan, New Delhi 110029, India.
Life Sci. 2020 Nov 15;261:118349. doi: 10.1016/j.lfs.2020.118349. Epub 2020 Aug 24.
Cerebral ischemic stroke leads to mitochondrial alterations which are key factors for initiation of various cascades resulting in neuronal damage. Dopamine D2 receptor (D2R) agonist, Sumanirole (SUM) has been reported to possess anti-inflammatory, anti-oxidant, and anti-apoptotic properties. However, the role of SUM in ischemic stroke (IS) has not been studied yet. The aim of the present study was to investigate the neuroprotective efficiency of SUM against ischemic injury and its possible effect on mitochondrial restorative mechanisms.
Transient middle cerebral artery occlusion (tMCAO) was performed in Wistar rats for 90 min occlusion and 22.5 h reperfusion to mimic ischemic stroke. Post- treatment with Sumanirole (0.1 mg/kg and 1 mg/kg; s.c.) was done at 1 h, 6 h, 12 hand 18 h after surgery. In addition, neurobehavioral analysis, mitochondrial reactive oxygen species and mitochondrial membrane potential by flow cytometric analysis, mitochondrial complexes analysis, infarct size evaluation and histological analysis were performed.
Sumanirole restored behavioural alterations as measured by rotarod performance, grip strength, adhesive tape removal analysis and neurological deficits. In addition, it also refurbished mitochondrial dysfunction by decreasing mitochondrial reactive oxygen species production, elevating mitochondrial membrane potential and by protecting the activity of mitochondrial complexes along with histological alterations. As a result, infarct sizes were markedly reduced in tMCAO surgery animals.
Findings from the study provide evidence that SUM promotes neuronal survival in in vivo model of IS through mitochondria mediated neuroprotective features.
脑缺血性中风导致线粒体改变，这是引发各种级联反应导致神经元损伤的关键因素。多巴胺 D2 受体（D2R）激动剂 SUMANIROLE（SUM）已被报道具有抗炎、抗氧化和抗细胞凋亡特性。然而，SUM 在缺血性中风（IS）中的作用尚未得到研究。本研究旨在探讨 SUM 对抗缺血性损伤的神经保护效率及其对线粒体修复机制的可能影响。
对 Wistar 大鼠进行短暂性大脑中动脉闭塞（tMCAO）手术，闭塞 90 分钟，再灌注 22.5 小时，模拟缺血性中风。术后 1 小时、6 小时、12 小时和 18 小时给予 SUMANIROLE（0.1 mg/kg 和 1 mg/kg；皮下注射）。此外，还进行了神经行为分析、流式细胞术分析测定线粒体活性氧和线粒体膜电位、线粒体复合物分析、梗死面积评估和组织学分析。
SUMANIROLE 通过旋转棒性能、握力、胶带去除分析和神经缺陷测量，恢复了行为改变。此外，它还通过减少线粒体活性氧的产生、提高线粒体膜电位以及保护线粒体复合物的活性来修复线粒体功能障碍，同时伴有组织学改变。因此，tMCAO 手术动物的梗死面积明显减少。
该研究结果提供了证据，表明 SUM 通过线粒体介导的神经保护特性在体内 IS 模型中促进神经元存活。
