title: 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: Department of Neuroscience, College of Medicine, Korea University, Seoul, Republic of Korea.
authors: Geum-Sil
authors: GS
authors: Cho
authors: Jae-Chul
authors: JC
authors: Lee
authors: Chung
authors: C
authors: Ju
authors: Chunsook
authors: C
authors: Kim
authors: Won-Ki
authors: WK
authors: Kim
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology* / Q000627:therapeutic use; D002544:Cerebral Infarction / Q000188:drug therapy* / Q000209:etiology / Q000473:pathology; D003337:Corpus Callosum / Q000187:drug effects* / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D007202:Indicators and Reagents; D020244:Infarction, Middle Cerebral Artery / Q000150:complications; D007249:Inflammation / Q000378:metabolism / Q000473:pathology; D007276:Injections, Intraventricular; D053583:Interleukin-1beta / Q000378:metabolism / Q000494:pharmacology; D002546:Ischemic Attack, Transient / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D008297:Male; D008559:Memantine / Q000494:pharmacology* / Q000627:therapeutic use; D008845:Microinjections; D037121:Plant Lectins; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*
chemical_list: D000893:Anti-Inflammatory Agents; C045475:Griffonia simplicifolia lectins; D007202:Indicators and Reagents; D053583:Interleukin-1beta; D037121:Plant Lectins; D016194:Receptors, N-Methyl-D-Aspartate; D016291:Dizocilpine Maleate; D008559:Memantine