کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2493787 1115528 2012 11 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Recombinant human MFG-E8 attenuates cerebral ischemic injury: Its role in anti-inflammation and anti-apoptosis
موضوعات مرتبط
علوم زیستی و بیوفناوری علم عصب شناسی علوم اعصاب رفتاری
پیش نمایش صفحه اول مقاله
Recombinant human MFG-E8 attenuates cerebral ischemic injury: Its role in anti-inflammation and anti-apoptosis
چکیده انگلیسی

Excessive inflammation and apoptosis contribute to the pathogenesis of ischemic stroke. MFG-E8 is a 66-kDa glycoprotein that has shown tissue protection in various models of organ injury. However, the potential role of MFG-E8 in cerebral ischemia has not been investigated. We found that levels of MFG-E8 protein in the brain were reduced at 24 h after cerebral ischemia. To assess the potential role of MFG-E8 in cerebral ischemia, adult male Sprague-Dawley rats were subjected to permanent middle cerebral artery occlusion (MCAO). At 1 h post-stroke onset, an intravenous administration of 1 ml saline as vehicle or 160 μg/kg BW recombinant human MFG-E8 (rhMFG-E8) as treatment was given. The optimal dose of rhMFG-E8 was obtained from previous dose–response organ protection in rat sepsis studies. Neurological scores were determined at 24 h and 48 h post-MCAO. Rats were sacrificed thereafter and brains rapidly removed and analyzed for infarct size, histopathology, and markers of inflammation and apoptosis. Compared with saline vehicle, rhMFG-E8 treatment led to significant decreases in sensorimotor and vestibulomotor deficits, and infarct size at 24 h and 48 h post-MCAO. Measures associated with improved outcome included reduced microglial inflammatory cytokine secretion, adhesion molecules and neutrophil influx, cleaved caspase-3, and upregulation of peroxisome proliferator activated receptor-γ (PPAR-γ), and Bcl-2/Bax ratio leading to decreased apoptosis. Thus, rhMFG-E8 treatment is neuroprotective against cerebral ischemia through suppression of inflammation and apoptosis.This article is part of a Special Issue entitled ‘Post-Traumatic Stress Disorder’.


► Inflammation and apoptosis contribute to the pathogenesis of cerebral infarction.
► rhMFG-E8 decreases infarct size and neurological deficits after cerebral ischemia.
► rhMFG-E8 suppresses cytokine release and apoptosis after cerebral ischemia.
► rhMFG-E8 is a novel neuroprotectant in cerebral ischemia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Neuropharmacology - Volume 62, Issue 2, February 2012, Pages 890–900
نویسندگان
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