کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
4344082 1615160 2013 6 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
N-Methyl-d-aspartate receptor antagonists memantine and MK-801 attenuate the cerebral infarct accelerated by intracorpus callosum injection of lipopolysaccharides
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب (عمومی)
پیش نمایش صفحه اول مقاله
N-Methyl-d-aspartate receptor antagonists memantine and MK-801 attenuate the cerebral infarct accelerated by intracorpus callosum injection of lipopolysaccharides
چکیده انگلیسی

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.


► Rats were subjected to MCAO 1 day after microinjection of LPS into corpus callosum.
► LPS pre-injection evoked inflammation and aggravated cerebral ischemic injury.
► LPS pre-injection enhanced the NMDA receptor-mediated neuronal calcium influx.
► NMDA receptor blockers reduced LPS-enhanced neuronal Ca2+ rise and ischemic injury.
► Inflammatory responses aggravate ischemic injury partly by enhancing excitotoxicity.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuroscience Letters - Volume 538, 22 March 2013, Pages 9–14
نویسندگان
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