Sistema endocannabinoide e endovanilloide nell'ischemia cerebrale

To furtherr investigate the role of endocannabinoid and endovanilloid system against neuronal injury in vivo, we injected exogenous compounds such as the cannabinoid agonist Delta9-tetrahydrocannabinol (THC) (0.05-2 mg/kg/i.p.), and the vanilloid agonist capsaicin (0.01-0.6 mg/kg/s.c.). The role of CB1 and VR1 receptors was investigated after treatment with rimonabant (0.05-3 mg/kg/i.p.) capsazepine (0.01-10 mg/kg/s.c.) respectively. Finally the effect of the anandamide transport inhibitor AM404 (0.03-2 mg/kg/i.p.) was studied. To quantify the ischemic damage we measured from 1 hour to 7 days after recirculation, electroencephalographic (EEG) mean total spectral power, spontaneous motor activity, cognitive function, rectal temperature and hippocampal neuronal count. These compounds showed a protective effect (versus vehicle treated group) against hyperlocomotion on Day 1, evaluated in an activity cage (p<0.01), memory impairment (passive avoidance test) on Day 3 (p<0.05) and EEG flattening (p<0.01) and neuronal loss (p<0.01) on Day 7. Taken together, these results showed that endocannabinoid and endovanilloid systems are closely connected suggesting that the modulation of AEA levels plays an important role in mechanisms underlying neuroprotection.