Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene receptor 2 antagonist, protects against acute brain injury after focal cerebral ischemia in rats
Intracerebroventricular injection of HAMI 3379, a selective cysteinyl leukotriene receptor 2 antagonist, protects against acute brain injury after focal cerebral ischemia in rats
复制标题
脑室内注射 HAMI 3379（一种选择性半胱氨酰白三烯受体 2 拮抗剂）可预防大鼠局灶性脑缺血后的急性脑损伤
DOI：
10.1016/j.brainres.2012.09.020
复制
发表时间：
2012-11-12
期刊：
影响因子：
2.9
通讯作者：
Wei, Er-Qing
中科院分区：
文献类型：
--
作者：
Shi, Qiao-Juan;Xiao, Li;Wei, Er-Qing
半胱氨酰白三烯（CysLTs）通过激活其受体CysLT（1）R和CysLT（2）R诱导炎症反应。我们最近报道了CysLT（2）R参与大鼠局灶性脑缺血后神经元损伤、星形胶质细胞增生和小胶质细胞增生。在这里，我们确定HAMI 3379，一种选择性CysLT（2）R拮抗剂，是否能保护大鼠局灶性脑缺血后的急性脑损伤。我们通过大脑中动脉闭塞（MCAO）30分钟，然后再灌注24小时来诱导短暂的局灶性脑缺血。将HAMI 3379（1、10或100 ng）脑室内（i. c. v.）30 min前，给予CysLT（1）R拮抗剂普仑司特（0.1 mg/kg，i. p.）用作阳性对照。HAMI 3379在10和100 ng（但不是在1 ng）减轻神经功能缺损，并减少梗死体积，脑水肿，IgG渗出，神经元变性和神经元丢失。这种保护作用与普仑司特相似。因此，10-100 ng i. c. v.的HAMI 3339对大鼠局灶性脑缺血后的急性脑损伤具有神经保护作用。这些发现表明CysLT（2）R拮抗剂在治疗缺血性卒中中具有治疗潜力。(C)2012爱思唯尔有限公司版权所有。
Cysteinyl leukotrienes (CysLTs) induce inflammatory responses by activating their receptors, CysLT(1)R and CysLT(2)R. We recently reported that CysLT(2)R is involved in neuronal injury, astrocytosis and microgliosis after focal cerebral ischemia in rats. Here, we determined whether HAMI 3379, a selective CysLT(2)R antagonist, protects against acute brain injury after focal cerebral ischemia in rats. We induced transient focal cerebral ischemia by 30 min of middle cerebral artery occlusion (MCAO), followed by 24 h of reperfusion. HAMI 3379 (1, 10 or 100 ng) was injected intracerebroventricularly (i.c.v.) 30 min before MCAO, and the CysLT(1)R antagonist pranlukast (0.1 mg/kg, i.p.) was used as a positive control. HAMI 3379 at 10 and 100 ng (but not at 1 rig) attenuated the neurological deficits, and reduced infarct volume, brain edema, IgG exudation, neuronal degeneration and neuronal loss. This protective effect was similar to that of pranlukast. Thus, HAMI 3339 at 10-100 ng i.c.v. is neuroprotective against acute brain injury after focal cerebral ischemia in rats. These findings suggest therapeutic potential for CysLT(2)R antagonists in the treatment of ischemic stroke. (C) 2012 Elsevier B.V. All rights reserved.