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 antagonist GV150526 was assessed in the middle artery occlusion (MCAo) model of focal ischemia. Postischemia administration of GV150526 (3 mg/kg i.v.) 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 determined by somatosensory evoked potential (SEP) responses recorded from the primary somatosensory cortex of rats under urethane anesthesia. Experimental occlusion of the MCA 7 days prior to electrophysiological testing induced a clear reduction in the SEP amplitude. GV150526 (3mg/kg, i.v.) was able to protect SEP responses recorded from the hindpaw cortical 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 field, an area closer to the core of the ischemic damage, were significantly protected only in the group treated 1 h post-MCAo. Histological evaluation 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 able to prevent the ischemic damage assessed histologically and affect the functional correlates of the ischemia evaluated by the electrophysiological SEP measurements.
Bordi
F
F
Pharmacology Department, GlaxoWellcome Research Laboratories, Verona, Italy.
Pietra
C
C
Ziviani
L
L
Reggiani
A
A
D000818:Animals; D001157:Arterial Occlusive Diseases / Q000188:drug therapy / Q000503:physiopathology; D002545:Brain Ischemia / Q000188:drug therapy* / Q000503:physiopathology; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000503:physiopathology; D004195:Disease Models, Animal; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D005073:Evoked Potentials, Somatosensory / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D005552:Forelimb; D018684:Glycine Agents / Q000494:pharmacology*; D006614:Hindlimb; D007211:Indoles / Q000494:pharmacology*; D008297:Male; D018696:Neuroprotective Agents / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors; D013003:Somatosensory Cortex / Q000098:blood supply / Q000473:pathology / Q000503:physiopathology
C105319:3-(2-((phenylamino)carbonyl)ethenyl)-4,6-dichloroindole-2-carboxylic acid; D018691:Excitatory Amino Acid Antagonists; D018684:Glycine Agents; D007211:Indoles; D018696:Neuroprotective Agents; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate