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

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 Ca(2+) 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.

• Authors: Geum-Sil Cho, Jae-Chul Lee, Chung Ju, Chunsook Kim, Won-Ki Kim
• Journal: Neuroscience letters (Neurosci Lett) Vol. 538 Pg. 9-14 (Mar 22 2013) ISSN: 1872-7972 [Electronic] Ireland
• PMID: 23376060 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Anti-Inflammatory Agents
• Griffonia simplicifolia lectins
• Indicators and Reagents
• Interleukin-1beta
• Plant Lectins
• Receptors, N-Methyl-D-Aspartate
• Dizocilpine Maleate
• Memantine

Topics

• Animals
• Anti-Inflammatory Agents (pharmacology, therapeutic use)
• Cerebral Infarction (drug therapy, etiology, pathology)
• Corpus Callosum (drug effects, metabolism)
• Dizocilpine Maleate (pharmacology, therapeutic use)
• Drug Synergism
• Indicators and Reagents
• Infarction, Middle Cerebral Artery (complications)
• Inflammation (metabolism, pathology)
• Injections, Intraventricular
• Interleukin-1beta (metabolism, pharmacology)
• Ischemic Attack, Transient (drug therapy, etiology, pathology)
• Male
• Memantine (pharmacology, therapeutic use)
• Microinjections
• Plant Lectins
• Rats
• Rats, Sprague-Dawley
• Receptors, N-Methyl-D-Aspartate (antagonists & inhibitors)