Anti-inflammatory property of the cannabinoid receptor-2-selective agonist in spinal cord injury (35.11)

Abstract

Abstract Recently cannabinoids are being studied in treatment of various animal models of CNS disorders such as MS, AD, PD and stroke. They are also being used in treating neuropathic pain in patients with spinal cord injury (SCI). Two cannabinoid receptors have been cloned; CB1, mainly expressed in the CNS and CB2, predominantly expressed in the periphery including immune cells. Previous studies from our laboratory showed that treatment with the CB2 specific agonist O-1966 improved recovery of motor and bladder function in mouse model of acute spinal cord injury. In SCI, increased infiltration and activation of inflammatory immune cells that follow the initial injury exacerbate neuronal damage. In this study we analyzed expression of inflammatory molecules that serve as markers for activation and infiltration of immune cells and their modulation by the CB2 agonist treatment. A murine thoracic spinal cord contusion model of SCI was used and spinal cords were analyzed for expression of various cytokines and chemokines. We found suppression of a number of molecules in spinal cords that were subjected to the CB2 agonist treatment. There was decreased expression of the CXCL family chemokine members CXCL1, 2, 3, 9 and 11, the CC family chemokine members CCL 8, 11, 20, T cell activation cytokines: IFN-γ, IL-23, IL-22 and some of the Toll-like receptors such as TLR1, 4, 6, and 7. Thus, it appears that CB2 agonist treatment may aid in recovery in acute SCI via its immunomodulating effects.