Sharma Poonam, Kulkarni G T, Sharma Bhupesh
Department of Pharmacology, Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India.
Amity Institute of Pharmacy, Amity University Uttar Pradesh, Noida, India.
Brain Res. 2020 Dec 1;1748:147116. doi: 10.1016/j.brainres.2020.147116. Epub 2020 Sep 11.
Ischemic stroke is a medical condition that arises because of poor blood supply to the brain. Reperfusion being salvage to the brain further causes, exacerbation of tissue injury, known as reperfusion injury. Ischemic preconditioning (IPC) has been known to provide benefits against ischemia reperfusion (I/R) injury. Dopamine D2/D3 receptor mediated several pathways are also reported as mediators in the IPC mediated neuroprotection. This study investigates the possible involvement of D2/D3 receptor activation in IPC mediated neuroprotection in the I/R brain. Global cerebral ischemia/reperfusion (GCI/R) injury in swiss albino mice was induced by occluding the common carotid arteries for 17 min, followed by 24 h reperfusion. IPC was provided by giving 3 episodes of I/R prior to Ischemia (17 min). Morris water maze (MWM) was used to assess the spatial learning, memory and Rota rod, lateral push test as well as inclined beam test were conducted to assess the motor functions in animals. Cerebral oxidative markers (thiobarbituric acid reactive species-TBARS, reduced glutathione-GSH, superoxide dismutase-SOD, and catalase-CAT), inflammatory markers (IL-6, IL-10, TNF-α, and myeloperoxidase-MPO), acetylcholinesterase activity-AChE, infarct size (% weight and % volume), and histopathological changes were also assessed. Haloperidol (0.05 mg/kg, i.p) was used to antagonize the effects of D2/D3 receptor activation. I/R animals showed reduction in memory, motor function, increase in cerebral oxidative stress, inflammation, AChE activity, infarct size and histopathological changes. Episodes of IPC prior to ischemia, attenuated the deleterious effects of I/R injury. Administration of haloperidol abolished the protective effects of IPC. Hence, it may be concluded that IPC mediated neuroprotection may involves dopamine D2/D3 receptor activation in mice.
缺血性中风是一种由于大脑血液供应不足而引发的病症。再灌注虽对大脑有挽救作用，但进一步会导致组织损伤加剧，即所谓的再灌注损伤。已知缺血预处理（IPC）对缺血再灌注（I/R）损伤有益。多巴胺D2/D3受体介导的多条通路也被报道为IPC介导神经保护作用的介质。本研究调查D2/D3受体激活在I/R脑内IPC介导的神经保护中可能发挥的作用。通过阻断瑞士白化小鼠的双侧颈总动脉17分钟，随后再灌注24小时，诱导全脑缺血/再灌注（GCI/R）损伤。在缺血（17分钟）前给予3次I/R来进行IPC预处理。使用莫里斯水迷宫（MWM）评估空间学习和记忆能力，并进行转棒试验、侧向推挤试验以及倾斜梁试验来评估动物的运动功能。还评估了脑氧化标志物（硫代巴比妥酸反应性物质-TBARS、还原型谷胱甘肽-GSH、超氧化物歧化酶-SOD和过氧化氢酶-CAT）、炎症标志物（IL-6、IL-10、TNF-α和髓过氧化物酶-MPO）、乙酰胆碱酯酶活性-AChE、梗死面积（重量百分比和体积百分比）以及组织病理学变化。使用氟哌啶醇（0.05mg/kg，腹腔注射）拮抗D2/D3受体激活的作用。I/R动物表现出记忆减退、运动功能下降，脑氧化应激、炎症、AChE活性、梗死面积和组织病理学变化增加。缺血前的IPC预处理减轻了I/R损伤的有害影响。给予氟哌啶醇消除了IPC的保护作用。因此，可以得出结论，IPC介导的神经保护作用可能涉及小鼠体内多巴胺D2/D3受体的激活。
