In vivo models of cerebral ischemia: effects of parenterally administered NMDA receptor glycine site antagonists.

Published

Journal Article

Both in vitro and in vivo experiments have implicated extracellular glycine in the pathogenesis of ischemic brain damage. Recently, halogenated derivatives of quinoxaline-2,3-dione have been synthesized that possess bioavailability when parenterally administered and minimal psychotomimetic properties. Such compounds have allowed investigation into the efficacy of glycine receptor antagonism as a strategy for protection against cerebral ischemic insults. Rats underwent either 90 min of middle cerebral artery filament occlusion or 10 min of forebrain ischemia with recovery while receiving intraperitoneal injections of either a glycine receptor antagonist (ACEA-1021, ACEA-1031, or ACEA-1011) or vehicle (dimethyl sulfoxide). Both ACEA-1021 and ACEA-1031 reduced cerebral infarct volumes and were associated with a reduced incidence of hemiparesis resulting from MCA occlusion. ACEA-1011, administered in a smaller dose had no effect. In the forebrain ischemia model, glycine receptor antagonism had no effect on delayed neuronal necrosis in the hippocampal CA1 sector, neocortex, or caudoputamen. We conclude that pharmacologic antagonism of glycine at the strychnine-insensitive glycine receptor presents a neuroprotective profile similar to that previously observed for antagonists of glutamate at the N-methyl-D-aspartate complex with a potential for fewer side effects.

Full Text

Duke Authors

Cited Authors

  • Warner, DS; Martin, H; Ludwig, P; McAllister, A; Keana, JF; Weber, E

Published Date

  • March 1995

Published In

Volume / Issue

  • 15 / 2

Start / End Page

  • 188 - 196

PubMed ID

  • 7860652

Pubmed Central ID

  • 7860652

International Standard Serial Number (ISSN)

  • 0271-678X

Digital Object Identifier (DOI)

  • 10.1038/jcbfm.1995.24

Language

  • eng

Conference Location

  • United States