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 journalArticlepeer-review

14 Citations (Scopus)


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
Publication statusPublished - 2013 Mar 22

Bibliographical note

Funding Information:
This research was supported by grants from Brain Research Center of the 21st Century Frontier Research Program ( 2011K000267 ) and the Bio & Medical Technology Development Program ( 2011-0019440 ), Republic of Korea.


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

ASJC Scopus subject areas

  • General Neuroscience


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