| First Author | Panikashvili D | Year | 2005 |
| Journal | J Cereb Blood Flow Metab | Volume | 25 |
| Issue | 4 | Pages | 477-84 |
| PubMed ID | 15729296 | Mgi Jnum | J:112490 |
| Mgi Id | MGI:3656414 | Doi | 10.1038/sj.jcbfm.9600047 |
| Citation | Panikashvili D, et al. (2005) CB1 cannabinoid receptors are involved in neuroprotection via NF-kappa B inhibition. J Cereb Blood Flow Metab 25(4):477-84 |
| abstractText | We reported earlier that closed head injury (CHI) in mice causes a sharp elevation of brain 2-arachidonoylglycerol (2-AG) levels, and that exogenous 2-AG reduces brain edema, infarct volume and hippocampal death and improved clinical recovery after CHI. The beneficial effect of 2-AG was attenuated by SR141716A, a CB1 cannabinoid receptor antagonist, albeit at relatively high doses. In the present study, we further explored the role of CB1 receptors in mediating 2-AG neuroprotection. CB1 receptor knockout mice (CB1-/-) showed minor spontaneous recovery at 24 h after CHI, in contrast to the significant improvement in neurobehavioral function seen in wild-type (WT) mice. Moreover, administration of 2-AG did not improve neurological performance and edema formation in the CB1-/- mice. In addition, 2-AG abolished the three- to four-fold increase of nuclear factor kappaB (NF-kappa B) transactivation, at 24 h after CHI in the WT mice, while it had no effect on NF-kappaB in the CB1-/- mice, which was as high as in the WT vehicle-treated mice. We thus propose that 2-AG exerts its neuroprotection after CHI, at least in part, via CB1 receptor-mediated mechanisms that involve inhibition of intracellular inflammatory signaling pathways. |
