The Effect of the Glycine Site-Specific N-Methyl-d-Aspartate Antagonist ACEA1021 on Ischemic Brain Damage Caused by Acute Subdural Hematoma in the Rat

Eiji Tsuchida, Ross Bullock

Research output: Contribution to journalArticle

37 Scopus citations

Abstract

Acute subdural hematoma (SDH) complicates about 20% of severely head- injured patients, and death and severe disability frequently result, yet over half of these patients may have been conscious, at some time after injury, implying secondary mechanisms of brain damage. Drugs that block the 'excitotoxic' effects of glutamate at the N-methyl-D-aspartate (NMDA) receptor have generally been effective in reducing ischemic brain damage associated with SDH in animal models, yet these agents all appear to be associated with major behavioral side effects, in conscious patients, at neuroprotective doses. We therefore evaluated the effects of treatment with a novel antagonist for the glycine binding site of the NMDA receptor (ACEA1021) upon ischemic brain damage, in the rat SDH model. ACEA1021 may be free of psychomotor effects, and may thus permit high dose therapy in conscious trauma and stroke patients. SDH was produced by the slow injection of 0.4 mL autologous blood into the subdural space overlying the parietal cortex. Brain damage was assessed histologically at 8 coronal planes, in animals sacrificed 4 h after induction of hematoma. Both pre and posttreatment with ACEA1021 significantly reduced hemispheric ischemic damage produced by SDH. The magnitude of neuroprotection with this compound (26 to 39% reduction in infarct size) is similar to other NMDA antagonists, and the robust posttreatment effect implies that human studies with this compound should be performed in head injured patients, subject to completion of toxicology testing.

Original languageEnglish (US)
Pages (from-to)279-288
Number of pages10
JournalJournal of neurotrauma
Volume12
Issue number3
DOIs
StatePublished - Jun 1995

Keywords

  • ACEA 1021
  • acute subdural hematoma
  • glycine binding site
  • ischemic brain damage
  • NMDA antagonist
  • rat

ASJC Scopus subject areas

  • Clinical Neurology
  • Neuroscience(all)

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