An endogenous cannabinoid (2-AG) is neuroprotective after brain injury

David Panikashvili, Constantina Simeonidou, Shimon Ben-Shabat, Lumír Hanuš, Aviva Breuer, Raphael Mechoulam and Esther Shohami ()
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David Panikashvili: Medical Faculty, Hebrew University
Constantina Simeonidou: Medical Faculty, Hebrew University
Shimon Ben-Shabat: Medical Faculty, Hebrew University
Lumír Hanuš: Medical Faculty, Hebrew University
Aviva Breuer: Medical Faculty, Hebrew University
Raphael Mechoulam: Medical Faculty, Hebrew University
Esther Shohami: Medical Faculty, Hebrew University

Nature, 2001, vol. 413, issue 6855, 527-531

Abstract: Abstract Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage1,2. Protective mechanisms to attenuate damage are also set in motion2. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery3 and in the brain4, but its physiological roles have been only partially clarified5,6,7. 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.

Date: 2001
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DOI: 10.1038/35097089

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