The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines

Endocannabinoids are involved in neuroprotection through numerous biochemical pathways. We have shown that the endocannabinoid 2-arachidonoyl glycerol (2-AG) is released in mouse brain after closed head injury (CHI), and treatment with exogenous 2-AC. exerts neuroprotection via the central cannabinoid receptor CB1. This process involves inhibition of inflammatory signals that are mediated by activation of the transcription factor NF-kappa B. The present study was designed to examine the effect of 2-AG on the blood-brain barrier (BBB) and the possible inhibition of the early expression of proinflammatory cytokines, which are implicated in BBB disruption. We found that 2-AG decreased BBB permeability and inhibited the acute expression of the main proinflammatory cytokines: TNF-alpha, IL-1 beta and IL-6. It also augmented the levels of endogenous antioxidants. We suggest that 2-AG exerts neuroprotection in part by inhibition of the early (1-4 h) inflammatory response and augmentation of the brain reducing power. (c) 2005 Elsevier Inc. All rights reserved.