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

David Panikashvili, Na'ama A. Shein, Raphael Mechoulam, Victoria Trembovler, Ron Kohen, Alexander Alexandrovich, Esther Shohami*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

184 Scopus citations

Abstract

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-AG 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-kB. 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-α, IL-1β 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.

Original languageAmerican English
Pages (from-to)257-264
Number of pages8
JournalNeurobiology of Disease
Volume22
Issue number2
DOIs
StatePublished - May 2006

Keywords

  • BBB integrity
  • Cytokines
  • Endocannabinoids
  • Inflammation
  • Neuroprotection
  • Reactive oxygen species
  • Traumatic brain injury

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