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

David Panikashvili, Constantina Simeonidou, Shimon Ben-Shabat, Lumír Hanuš, Aviva Breuer, Raphael Mechoulam, Esther Shohami

Research output: Contribution to journalArticlepeer-review

614 Scopus citations

Abstract

Traumatic brain injury triggers the accumulation of harmful mediators that may lead to secondary damage. Protective mechanisms to attenuate damage are also set in motion. 2-Arachidonoyl glycerol (2-AG) is an endogenous cannabinoid, identified both in the periphery and in the brain, but its physiological roles have been only partially clarified. 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.

Original languageEnglish
Pages (from-to)527-531
Number of pages5
JournalNature
Volume413
Issue number6855
DOIs
StatePublished - 4 Oct 2001
Externally publishedYes

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