N-acetylaspartylglutamate protects against transient focal cerebral ischemia in rats

Xi Chun M. Lu, Zhaocheng Tang, Weilin Liu, Qian Lin, Barbara S. Slusher

Research output: Contribution to journalArticlepeer-review

Abstract

The inhibition of N-acetylated α-linked acidic dipeptidase (NAALADase: glutamate carboxypeptidase II) has been previously shown to protect against ischemic injury presumably through mechanisms of decreasing glutamate and increasing N-acetylaspartylglutamate (NAAG). Preventing excessive glutamate release is known to be neuroprotective. However, the role of increased NAAG is not clear. We used a middle cerebral artery occlusion model in rats to investigate the neuroprotective effect of NAAG via its action as a metabotropic glutamate (mGlu) receptor agonist. Rats received intracerebral injections of NAAG (1, 2, or 4 μmol), or a co-injection of NAAG (2 μmol) and the non-selective mGlu receptor antagonist, (R,S)-α-methyl-4-carboxyphenylglycine, (MCPG, 2 μmol). Immediately after the treatment, the animals received 2 h of middle cerebral artery occlusion followed by 22 h of reperfusion. Treatment with 1 or 2 μmol of NAAG significantly reduced total infarct volume. Treatment with MCPG partially attenuated the neuroprotective effect of NAAG, indicating that the protective effect of NAAG against ischemic injury may be in part mediated via activation of mGlu receptors. Copyright (C) 2000 Elsevier Science B.V.

Original languageEnglish (US)
Pages (from-to)233-239
Number of pages7
JournalEuropean Journal of Pharmacology
Volume408
Issue number3
DOIs
StatePublished - Nov 24 2000
Externally publishedYes

Keywords

  • Ischemia
  • MCPG ((R,S)-α-methyl-4-carboxyphenylglycine)
  • NAAG (N-acetylaspartylglutamate)
  • NAALADase (N-acetylated α-linked acidic dipeptidase)
  • mGlu receptor

ASJC Scopus subject areas

  • Pharmacology

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