An endogenous cannabinoid (2-AG) is neuroprotective after brain injury
An endogenous cannabinoid (2-AG) is neuroprotective after brain injury
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DOI：
10.1038/35097089
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发表时间：
2001-10-04
期刊：
影响因子：
64.8
通讯作者：
Shohami, E
中科院分区：
文献类型：
--
作者：
Panikashvili, D;Simeonidou, C;Shohami, E
创伤性脑损伤触发有害介质的积累，可能导致继发性损伤（1，2）。保护机制，以减轻损害也设置在运动（2）。2-花生四烯酰甘油（2-AG）是一种内源性大麻素，在外周（3）和大脑（4）中都有发现，但其生理作用仅得到部分阐明（5-7）。在这里，我们表明，在小鼠大脑损伤后，2-AG可能具有神经保护作用，其中大麻素系统参与其中。小鼠闭合性颅脑损伤后内源性2-AG水平明显升高。我们在CHI后给小鼠施用合成的2-AG，发现与对照组相比，脑水肿显著减少，临床恢复更好，梗死体积减少，海马细胞死亡减少。当2-AG与通常存在于脑中的额外的无活性2-酰基甘油一起施用时，功能恢复显著增强。SR-141761 A（CB 1大麻素受体拮抗剂）剂量依赖性地减弱2-AG的有益作用。
Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage(1,2). Protective mechanisms to attenuate damage are also set in motion(2). 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery(3) and in the brain(4), but its physiological roles have been only partially clarified(5-7). Here we show that, after injury to the mouse brain, 2-AG may have a neuroprotective role in which the cannabinoid system is involved. After closed head injury (CHI) in mice, the level of endogenous 2-AG was significantly elevated. We administered synthetic 2-AG to mice after CHI and found significant reduction of brain oedema, better clinical recovery, reduced infarct volume and reduced hippocampal cell death compared with controls. When 2-AG was administered together with additional inactive 2-acyl-glycerols that are normally present in the brain, functional recovery was significantly enhanced. The beneficial effect of 2-AG was dose-dependently attenuated by SR-141761A, an antagonist of the CB1 cannabinoid receptor.