Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats
Progesterone is neuroprotective after transient middle cerebral artery occlusion in male rats
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DOI：
10.1016/0006-8993(96)00605-1
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发表时间：
1996-09-30
期刊：
影响因子：
2.9
通讯作者：
Feit, H
中科院分区：
文献类型：
--
作者：
Jiang, N;Chopp, M;Feit, H
黄体酮（FROG）是一种神经类固醇，在中枢神经系统中具有多种功能。外源性FROG已被证明可以减少脑挫伤后的继发性神经元损失，同时减轻脑水肿，并减少局灶性脑缺血后的脑水肿。在本研究中，我们在大鼠局灶性脑缺血模型中评估了蛙的神经保护潜力。48只雄性Wistar大鼠随机分为4组，分别用水溶性FROG或二甲基亚砜（DMSO）溶解FROG进行预处理，或用DMSO作为对照，或用DMSO溶解FROG进行延迟处理。采用腔内缝合线诱导大脑中动脉闭塞，取出缝合线进行再灌注。在MCAO前30分钟通过腹腔注射进行预处理。MCAO 2小时后再灌注延迟治疗。MCAO 48小时后测量梗死体积、体重减轻和神经功能缺损。与对照动物相比，DMSO溶解FROG治疗前和延迟治疗分别使脑梗死减少39% （P < 0.05）和34% (P < 0.05)，同时体重减轻和神经功能改善，而水溶性FROG治疗未发现梗死体积减少有统计学意义。我们证明，在MCAO发作前或2小时后给予雄性大鼠FROG可减少缺血性细胞损伤，并在中风后2天改善生理和神经功能。这些结果提示FROG在脑卒中治疗中的潜在治疗特性。
Progesterone (FROG) is a neurosteroid, possessing a variety of functions in the central nervous system. Exogenous FROG has been shown to reduce secondary neuronal loss in conjunction with attenuated brain edema after cerebral contusion and to reduce brain edema after focal cerebral ischemia. In the present study, we assessed the neuroprotective potential of FROG in a model of focal cerebral ischemia in the rat. Forty-eight male Wistar rats were randomly assigned to 4 groups, i.e. pretreatment with water soluble FROG, or dimethyl sulfoxide (DMSO) dissolved FROG, or DMSO as control or delayed treatment with DMSO dissolved FROG. Middle cerebral artery occlusion (MCAO) was induced by insertion of an intraluminal suture and reperfusion was performed by withdrawing the suture. Pretreatments were initiated 30 min before MCAO via intraperitoneal injection. Delayed treatment was initiated upon reperfusion following 2 h of MCAO. Infarct volume, body weight loss, and neurological deficit were measured 48 h after MCAO. Pre- and delayed treatment with DMSO dissolved FROG resulted in a 39% (P < 0.05) and 34% (P < 0.05) reduction in cerebral infarction, respectively, along with decreased body weight loss and improved neurological function as compared to control animals, whereas no statistically significant reduction in infarct volume by water soluble FROG was found. We demonstrated that administration of FROG to the male rat before or 2 hours after onset of MCAO reduces ischemic cell damage and improves physiological and neurological function 2 days after stroke. These results suggests potential therapeutic properties of FROG in the management of stroke.