1-Aminoindan-1,5-dicarboxylic acid and (S)-(+)-2-(3'-carboxybicyclo[1.1.1] pentyl)-glycine, two mGlu1 receptor-preferring antagonists, reduce neuronal death in in vitro and in vivo models of cerebral ischaemia.

摘要: Metabotropic glutamate (mGlu) receptors have been implicated in a number of physiological and pathological responses to glutamate, but the exact role group I mGlu causing postischaemic injury is not yet clear. In this study, we examined whether recently-characterized relatively selective mGlu1 receptor antagonists 1-aminoindan-1,5-dicarboxylic acid (AIDA) (S)-(+)-2-(3'-carboxybicyclo[1.1.1]pentyl)-glycine (CBPG) could reduce neuronal death vitro, following oxygen-glucose deprivation (OGD) murine cortical cell rat organotypic hippocampal cultures, vivo, after global ischaemia gerbils. When present incubation medium during OGD insult subsequent 24 h recovery period, AIDA CBPG significantly reduced vitro. The extent protection was similar that observed with nonselective antagonist (+)-alpha-methyl-4-carboxyphenylglycine [(+)MCPG] typical ionotropic (iGlu) antagonists. Neuroprotection also when or were added only terminated. Neuronal attenuated by inactive isomer (-)MCPG, enhanced agonist (1S,3R)-1-aminocyclopentane-1, 3-dicarboxylic [(1S,3R)-ACPD] 3,5-dihydroxyphenylglycine (3,5-DHPG). (+)MCPG, neuroprotective because i. c.v. administration CA1 pyramidal degeneration 7 days transient carotid occlusion Our results point mechanisms responsible for propose new target neuroprotection.