THE GLYCINE ANTAGONIST GV150526 PROTECTS SOMATOSENSORY-EVOKED POTENTIALS AND REDUCES THE INFARCT AREA IN THE MCAO MODEL OF FOCAL ISCHEMIA IN THE RAT

The neuroprotective activity of the novel, selective glycine antagonis t GV150526 was assessed in the middle artery occlusion (MCAo) model of focal ischemia. Postischemia administration of GV150526 (3 mg/kg iv) up to 6 h post-MCAo resulted in a significant reduction of the infarct volume measured histologically 24 h later. The neuronal protection by GV150526 was accompanied by functionally significant protection deter mined by somatosensory evoked potential (SEP) responses recorded from the primary somatosensory cortex of rats under urethane anesthesia. Ex perimental occlusion of the MCA 7 days prior to electrophysiological t esting induced a clear reduction in the SEP amplitude. GV150526 (3mg/k g, iv) was able to protect SEP responses recorded from the hindpaw cor tical field in two groups of animals treated either 1 (n = 9) or 6 h ( n = 10) post-MCAo. SEP responses recorded from the forepaw cortical fi eld, an area closer to the core of the ischemic damage, were significa ntly protected only in the group treated 1 h post-MCAo. Histological e valuation of the rat brain regions showed a correlated decrease in the ischemic area of GV150526-treated groups. The volumes of the ischemic brains of both GV150526 groups were statistically different from the MCAo group (P < 0.05). These findings demonstrate that GV150526 is abl e to prevent the ischemic damage assessed histologically and affect th e functional correlates of the ischemia evaluated by the electrophysio logical SEP measurements. (C) 1997 Academic Press.