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

doi:10.1016/j.nbd.2005.11.004

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

School of Pharmacy

Research output: Contribution to journal › Article › peer-review

179 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 language	American English
Pages (from-to)	257-264
Number of pages	8
Journal	Neurobiology of Disease
Volume	22
Issue number	2
DOIs	https://doi.org/10.1016/j.nbd.2005.11.004
State	Published - May 2006

Keywords

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

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10.1016/j.nbd.2005.11.004

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

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.",

keywords = "BBB integrity, Cytokines, Endocannabinoids, Inflammation, Neuroprotection, Reactive oxygen species, Traumatic brain injury",

author = "David Panikashvili and Shein, {Na'ama A.} and Raphael Mechoulam and Victoria Trembovler and Ron Kohen and Alexander Alexandrovich and Esther Shohami",

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AU - Mechoulam, Raphael

AU - Trembovler, Victoria

AU - Kohen, Ron

AU - Alexandrovich, Alexander

AU - Shohami, Esther

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N2 - 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.

AB - 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.

KW - BBB integrity

KW - Cytokines

KW - Endocannabinoids

KW - Inflammation

KW - Neuroprotection

KW - Reactive oxygen species

KW - Traumatic brain injury

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ER -

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

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Keywords

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