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

David Panikashvili*†, Constantina Simeonidou*, Shimon Ben-

Nature

Wednesday 03 Oct 2001

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* Department of Pharmacology, Medical Faculty,
Hebrew University, Jerusalem 91120, Israel
† Department of Medicinal Chemistry and Natural
Products, Medical Faculty, Hebrew University,
Jerusalem 91120, Israel

Nature 413, 527 - 531 (2001)



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.
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Nature © Macmillan Publishers Ltd 2001 Registered No. 785998


 

 

 

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