Capsaicin exhibits neuroprotective effects in a model of transient global cerebral ischemia in Mongolian gerbils

Capsaicin, the irritant principle of hot peppers, is a vanilloid agonist known to activate the transient receptor potential channel vanilloid subfamily member 1 (VR1), recently reported to be involved in neurodegeneration. The present study investigated the role of VR1 in a model of global cerebral ischemia in gerbils. Over the dose range tested, capsaicin (0.01, 0.025, 0.05, 0.2 and 0.6 mg kg ^-1), given 5 min after recirculation, dose-dependently antagonized the ischemia-induced electroencephalographic total spectral power decrease and restored relative frequency band distribution evaluated 7 days after ischemia. Capsaicin, at all tested doses, fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia. Capsaicin dose-dependently antagonized ischemia-induced memory impairment evaluated in a passive avoidance task, 3 days after ischemia. Capsaicin showed a dose-dependent hypothermic effect evaluated for 2 h after recirculation. At 7 days after ischemia, a progressive survival of pyramidal cells in the CA1 subfield in capsaicin-treated gerbils, with a maximum of 80%, at a dose of 0.2 mg kg ^-1, was obtained. The selective VR1 antagonist, capsazepine (0.01 mg kg ^-1), reversed capsaicin-induced protective effects, in a competitive manner. These results suggest that the neuroprotective effect of capsaicin may be attributable, at least in part, to VR1 desensitizadon and provide a valuable target for development of interventional pharmacological strategies.