N-Methyl-d-aspartate receptor antagonists memantine and MK-801 attenuate the cerebral infarct accelerated by intracorpus callosum injection of lipopolysaccharides

Geum Sil Cho, Jae Chul Lee, Chung Ju, Chunsook Kim, Won Ki Kim

Research output: Contribution to journalArticle

11 Citations (Scopus)

Abstract

Inflammatory responses have been shown to modulate the pattern and degree of ischemic injury. Previously, we demonstrated that intracorpus callosum microinjection of lipopolysaccharide (LPS, a well-known endotoxin) markedly induced inflammatory responses confined to ipsilateral hemisphere and aggravated cerebral ischemic injury. Here we report that LPS injection increases the degree of N-methyl-d-aspartate (NMDA) receptor-mediated excitotoxicity, one of major causes of cerebral ischemic injury. Intracorpus callosum microinjection of LPS 1 day prior to ischemic insults augmented intraneuronal Ca2+ rise in rat brains subjected to transient occlusion of middle cerebral artery. Intraperitoneal administration of memantine, a NMDA receptor antagonist, reduced the LPS-enhanced calcium response as well as ischemic tissue damage. Western blot and immunohistochemistry data showed that the level of IL-1β was enhanced in LPS-injected rat brains, particularly in isolectin-B4 immunoreactive cells. Intraventricular microinjection of recombinant rat IL-1β aggravated cerebral ischemic injury, which was significantly reduced by memantine. Intraventricular injection of anti-IL-1β antibody significantly reduced the cerebral infarction aggravated by LPS preinjection. The results indicate that IL-1β released from isolectin-B4 immunoreactive cells enhanced excitotoxicity, consequently aggravating ischemic brain injury.

Original languageEnglish
Pages (from-to)9-14
Number of pages6
JournalNeuroscience Letters
Volume538
DOIs
Publication statusPublished - 2013 Mar 22

    Fingerprint

Keywords

  • Excitotoxicity
  • Interleukin-1β
  • Ischemia
  • Lipopolysaccharides
  • Memantine
  • Middle cerebral artery occlusion
  • N-Methyl-d-aspartate
  • Stroke

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this