TY - JOUR
T1 - The endocannabinoid 2-AG protects the blood-brain barrier after closed head injury and inhibits mRNA expression of proinflammatory cytokines
AU - Panikashvili, David
AU - Shein, Na'ama A.
AU - Mechoulam, Raphael
AU - Trembovler, Victoria
AU - Kohen, Ron
AU - Alexandrovich, Alexander
AU - Shohami, Esther
PY - 2006/5
Y1 - 2006/5
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
UR - http://www.scopus.com/inward/record.url?scp=33646142292&partnerID=8YFLogxK
U2 - 10.1016/j.nbd.2005.11.004
DO - 10.1016/j.nbd.2005.11.004
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C2 - 16364651
AN - SCOPUS:33646142292
SN - 0969-9961
VL - 22
SP - 257
EP - 264
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 2
ER -