Chitkara College of Pharmacy, Chandigarh-Patiala National Highway, Rajpura, 140 401 Patiala, Punjab, India.
Cytokine. 2012 Oct;60(1):83-9. doi: 10.1016/j.cyto.2012.05.009. Epub 2012 Jun 15.
The present study has been designed to investigate the potential role of CCR-2 chemokine receptor in ischemic preconditioning as well as postconditioning induced reversal of ischemia-reperfusion injury in mouse brain. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24h was employed in present study to produce ischemia and reperfusion induced cerebral injury in mice. Cerebral infarct size was measured using triphenyltetrazolium chloride staining. Memory was evaluated using elevated plus-maze test and Morris water maze test. Rota rod test was employed to assess motor incoordination. Bilateral carotid artery occlusion followed by reperfusion produced cerebral infarction and impaired memory and motor co-ordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min were employed to elicit ischemic preconditioning of brain, while three episodes of bilateral carotid artery occlusion for 10s and reperfusion of 10s immediately after the completion of were employed to elicit ischemic postconditioning of brain. Both prior ischemic preconditioning as well as ischemic postconditioning immediately after global cerebral ischemia prevented markedly ischemia-reperfusion-induced cerebral injury as measured in terms of infarct size, loss of memory and motor coordination. RS 102895, a selective CCR-2 chemokine receptor antagonist, attenuated the neuroprotective effect of both the ischemic preconditioning as well as postconditioning. It is concluded that the neuroprotective effect of both ischemic preconditioning as well as ischemic postconditioning may involve the activation of CCR-2 chemokine receptors.
本研究旨在探讨 CCR-2 趋化因子受体在缺血预处理以及后处理诱导的小鼠脑缺血再灌注损伤逆转中的潜在作用。本研究采用双侧颈总动脉闭塞 17 分钟，再灌注 24 小时的方法，在小鼠中产生缺血再灌注诱导的脑损伤。采用氯化三苯基四氮唑染色测量脑梗死面积。采用高架十字迷宫试验和 Morris 水迷宫试验评估记忆。采用转棒试验评估运动协调能力。双侧颈总动脉闭塞再灌注可导致脑梗死、记忆和运动协调能力受损。采用 3 次双侧颈总动脉闭塞 1 分钟和再灌注 1 分钟的预处理来诱导脑缺血预处理，采用 3 次双侧颈总动脉闭塞 10 秒和再灌注 10 秒的后处理来诱导脑缺血后处理。在全脑缺血后立即进行的这两种预处理和后处理均可显著预防缺血再灌注引起的脑损伤，如梗死面积、记忆和运动协调能力的丧失。CCR-2 趋化因子受体的选择性拮抗剂 RS 102895 减弱了缺血预处理和后处理的神经保护作用。结论：缺血预处理和后处理的神经保护作用可能涉及 CCR-2 趋化因子受体的激活。
