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Endocannabinoids and Traumatic Brain Injury

Molecular Neurobiology volume 36, pages 68–74 (2007)Cite this article

Abstract

In response to traumatic brain injury, there is local and transient accumulation of 2-AG at the site of injury, peaking at 4 h and sustained up to at least 24 h. Neuroprotection exerted by exogenous 2-AG suggests that the formation of 2-AG may serve as a molecular regulator of pathophysiological events, attenuating the brain damage. Inhibition of this protective effect by SR-141716A, a CB1 cannabinoid receptor antagonist, and the lack of effect of 2-AG in CB1 knockout mice suggest that 2-AG and the CB1 receptor may be important in the pathophysiology of traumatic brain injury. 2-AG exerts its neuroprotective effect after traumatic brain injury, at least in part, by inhibition of NF-κB transactivation. 2-AG also inhibits, at an early stage (2–4 h), the expression of the main proinflammatory cytokines, TNF-α, IL-6, and IL-1β, and is accompanied by reduction of BBB permeability. Moreover, the CB1, CB2, and TRVP1 receptors are expressed on microvascular endothelial cells, and their activation by 2-AG counteracts endothelin (ET-1)-induced cerebral microvascular responses (namely, Ca2+ mobilization and cytoskeleton rearrangement). This suggests that the functional interaction between 2-AG and ET-1 may provide a potential alternative pathway for abrogating ET-1-inducible vasoconstriction after brain injury and play a role in the neuroprotective effects exerted by 2-AG, as a potent vasodilator.

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Acknowledgements

We thank the US National Institute on Drug Abuse, the US-Israel Binational Foundation, and the Miriam and Sheldon Adelson Program in Neural Repair and Rehabilitation for generous support.

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Affiliations

  1. Department of Medicinal Chemistry and Natural Products, Hebrew University Medical Faculty, Ein Kerem campus, Jerusalem, 91120, Israel

    R. Mechoulam

  2. Department of Pharmacology, Hebrew University School of Pharmacy, Jerusalem, 91120, Israel

    E. Shohami

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  1. R. Mechoulam
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  2. E. Shohami
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Correspondence to R. Mechoulam.

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Mechoulam, R., Shohami, E. Endocannabinoids and Traumatic Brain Injury. Mol Neurobiol 36, 68–74 (2007). https://doi.org/10.1007/s12035-007-8008-6

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  • DOI: https://doi.org/10.1007/s12035-007-8008-6

Keywords

  • 2-AG
  • Blood–brain barrier
  • Brain endothelial cells
  • Cannabinoids
  • Cytokines
  • Endocannabinoids
  • NF-κB
  • TNF-α
  • Vasodilation