Memory restoring and neuroprotective effects of the proline-containing dipeptide, GVS-111, in a photochemical stroke model

Local thrombosis of the frontal cortex (Fr1 and Fr3 fields), caused by comb ination of the intravenous photosensitive dye Rose Bengal administration wi th focused high-intensity illumination of the frontal bone, was shown to pr ovoke a pronounced deficit in step-through passive avoidance performance in rats without concomitant motor disturbances. N-Phenylacetyl-L-prolylglycin e ethyl ester (GVS-111) administered intravenously at a dose of 0.5 mg/kg/d ay, for the first time 1 h after ischaemic lesion and then for 9 post-opera tive days, with the last administration 15 min before testing, attenuated t he deficit. This treatment significantly diminished the volume of the infar cted area. Thus, post-ischaemic injection of GVS-111 demonstrated both cogn ition-restoring and neuroprotective properties. The cognition-restoring eff ect is probably based on an increase in neocortical and hippocampal neurona l plasticity. Neuroprotective effects of GVS-111 combine antioxidant activi ty with the ability to attenuate glutamate-provoked neurotoxicity and block voltage gated ionic channels, i.e. the compound mitigates the main metabol ic shifts involved in pathogenesis of brain ischaemia. (C) 1999 Lippincott Williams & Wilkins.