Anandamide content is increased and Cb1 cannabinoid receptor blockade is protective during transient, focal cerebral ischemia
Anandamide content is increased and Cb1 cannabinoid receptor blockade is protective during transient, focal cerebral ischemia
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DOI：
10.1016/j.neuroscience.2004.08.044
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发表时间：
2004-01-01
期刊：
影响因子：
3.3
通讯作者：
Hillard, CJ
中科院分区：
文献类型：
--
作者：
Muthian, S;Rademacher, DJ;Hillard, CJ
内源性大麻素信号在大脑对损伤的反应中的作用是诱人的，但还不清楚。本研究采用短暂性大脑中动脉闭塞（MCAo）造成大鼠大脑缺血再灌注损伤。在MCAo期间测定N-花生四烯酸乙醇胺（AEA）和2-花生四烯酸甘油的脑含量。与假手术组相比，MCAo后30、60和120 min全脑AEA含量显著增加。AEA的增加局限于30分钟MCAo后的缺血半球，但在60和120分钟，也增加了对侧半球。2-花生四烯酰甘油含量不受MCAo的影响。在第二组研究中，在2 h MCAo后24 h评估损伤。与溶剂对照组相比，在MCAo之前给予单剂量（3 mg/kg）大麻素受体1型（CB 1）受体拮抗剂SR 141716的大鼠显示梗死体积减少50%，神经功能改善40%。第二种CB受体拮抗剂LY 320135（6 mg/kg）也显著改善了神经功能。CB 1受体激动剂WIN 55212-2（0.1-1 mg/kg）不影响梗死体积或神经评分。(C)2004年IBRO。由爱思唯尔有限公司发布。保留所有权利。
The of endocannabinoid signaling in the response of the brain to injury is tantalizing but not clear. In this study, transient middle cerebral artery occlusion (MCAo) was used to produce ischemia/reperfusion injury. Brain content of N-arachidonoylethanolamine (AEA) and 2-arachidonoylglycerol were determined during MCAo. Whole brain AEA content was significantly increased after 30, 60 and 120 min MCAo compared with sham-operated brain. The increase in AEA was localized to the ischemic hemisphere after 30 min MCAo, but at 60 and 120 min, was also increased in the contralateral hemisphere. 2-Arachidonoylglycerol content was unaffected by MCAo. In a second set of studies, injury was assessed 24 h after 2 h MCAo. Rats administered a single dose (3 mg/kg) of the cannabinoid receptor type 1 (CB1) receptor antagonist SR141716 prior to MCAo exhibited a 50% reduction in infarct volume and a 40% improvement in neurological function compared with vehicle control. A second CB, receptor antagonist, LY320135 (6 mg/kg), also significantly improved neurological function. The CB1 receptor agonist, WIN 55212-2 (0.1-1 mg/kg) did not affect either infarct volume or neurological score. (C) 2004 IBRO. Published by Elsevier Ltd. All rights reserved.