Rehni Ashish K, Bhateja Pradeep, Singh Nirmal, Jaggi Amteshwar S
Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala 147002, India.
Fundam Clin Pharmacol. 2008 Apr;22(2):179-88. doi: 10.1111/j.1472-8206.2008.00567.x.
The present study has been designed to pharmacologically investigate the role of mast cell degranulation in ischemic preconditioning-induced reversal of global ischemia- and reperfusion-induced cerebral injury in mice. Bilateral carotid artery occlusion of 17 min followed by reperfusion for 24 h 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 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 coordination. Three preceding episodes of bilateral carotid artery occlusion for 1 min and reperfusion of 1 min (ischemic preconditioning) prevented markedly ischemia-reperfusion-induced cerebral injury measured in terms of infarct size, loss of memory and motor coordination. Sodium cromoglycate (10 mg/kg, i.p.), a mast cell stabilizer attenuated the neuroprotective effect of ischemic preconditioning. It is concluded that neuroprotective effect of ischemic preconditioning may be due to the degranulation of mast cells.
本研究旨在从药理学角度探讨肥大细胞脱颗粒在缺血预处理诱导的小鼠全脑缺血及再灌注所致脑损伤逆转中的作用。本研究采用双侧颈动脉闭塞17分钟后再灌注24小时的方法,在小鼠中造成缺血及再灌注诱导的脑损伤。使用氯化三苯基四氮唑染色法测量脑梗死面积。采用莫里斯水迷宫试验评估记忆。采用转棒试验评估运动不协调。双侧颈动脉闭塞后再灌注导致了脑梗死,并损害了记忆和运动协调能力。之前三次双侧颈动脉闭塞1分钟并再灌注1分钟(缺血预处理)的情况,显著预防了以梗死面积、记忆丧失和运动协调能力衡量的缺血再灌注诱导的脑损伤。肥大细胞稳定剂色甘酸钠(10毫克/千克,腹腔注射)减弱了缺血预处理的神经保护作用。得出的结论是,缺血预处理的神经保护作用可能归因于肥大细胞的脱颗粒。