INFLAMMATORY RESPONSES Brain Injury Circumvented by Endocannabinoids

Abstract: Physiological responses to brain trauma, such as edema, are often much more injurious to the brain than the initial trauma event itself. Although intrinsic protective responses also occur subsequent to brain injury, the promotion of protection over pathological responses in such circumstances would help ameliorate irreversible brain damage. Panikashvili et al. studied brain trauma in mice and found that amounts of the endogenous cannabinoid 2-arachidonoyl glycerol (2-AG) were increased following brain injury and provided protection. Amounts of endogenous 2-AG in the brain peaked at 4 hours after trauma. Mice treated with exogenous 2-AG had less apoptosis in hippocampal neurons and reduced brain edema as compared with untreated animals, suggesting that 2-AG provided some protection from deleterious swelling. The neuroprotective effect of 2-AG was inhibited by treating injured brains with cannabinoid receptor 1 (CB1) antagonists, indicating that at least some neuroprotection was mediated by CB1. Protection was also enhanced by adding other endogenous substances that were thought to increase the receptor occupancy of CB1 by 2-AG. Thus, 2-AG, which is known to suppress the activation of tumor necrosis factor , a proinflammatory cytokine, and endothelin-1, a potent vasoconstrictor, appears to mediate a physiological protective response in brain injury. Augmentation of this response may further increase the observed protective effect.

D. Panikashvili, C. Simeonidou, S. Ben-Shabat, L. Hanu, A. Breuer, R. Mechoulam, E Shohami, An endogenous cannabinoid (2-AG) is neuroprotective after brain injury. Nature 413, 527-531 (2001). [Online Journal]