2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic strok

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Title:	2-Methoxystypandrone ameliorates brain function through preserving BBB integrity and promoting neurogenesis in mice with acute ischemic strok
Authors:	Chern, Chang-Mink Wang, Yea-Hwey Liou, Kuo-Tong Hou, Yu-Chang Chen, Chien-Chih Shen, Yuh-Chiang
Contributors:	國術學系
Keywords:	2-Methoxystypandrone (2MS) beta-Catenin doublecortin Glycogen synthase kinase 3 (GSK3) Ischemic stroke Subgranular zone (SGZ)
Date:	2014-02-01
Issue Date:	2015-01-27 13:50:32 (UTC+8)
Abstract:	2-Methoxystypandrone (2-MS), a naphthoquinone, has been shown to display an immunomodulatory effect in a cellular model. To explore whether 2-MS could protect mice against cerebral ischemic/reperfusion (I/R)-induced brain injury, we evaluated 2-MS's protective effects on an acute ischemic stroke by inducing a middle cerebral artery occlusion/reperfusion (MCAO) injury in murine model. Treatment of mice that have undergone I/R injury with 2-MS (10-100 mu g/kg, i.v.) at 2 h after MCAO enhanced survival rate and ameliorated neurological deficits, brain infarction, neural dysfunction and massive oxidative stress, due to an enormous production of free radicals and breakdown of blood-brain barrier (BBB) by I/R injury; this primarily occurred with extensive infiltration of CD11b-positive inflammatory cells and upexpression of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 and p65 nuclear factor-kappa B (NF-kappa B). All of these pathological changes were diminished by 2-MS; 2-MS also intensively limited cortical infarction and promoted upexpression of neurodevelopmental genes near pen-infarct cortex and endogenous neurogenesis near subgranular zone of hippocampal dentate gyms and the subventricular zone, most possibly by inactivation of GSK3 beta which in turn upregulating beta-catenin, Bcl-2 adam11 and adamts20. We conclude that 2-MS blocks inflammatory responses by impairing NF-kappa B signaling to limit the inflammation and oxidative stress for preservation of BBB integrity; 2-MS also concomitantly promotes neurodevelopmental protein expression and endogenous neurogenesis through inactivation of GM (3 to enhance beta-catenin signaling for upexpression of neuroprotective genes and proteins. (C) 2013 Elsevier Inc. All rights reserved.
Relation:	BIOCHEMICAL PHARMACOLOGY 卷: 87 期: 3 頁碼: 502-514
Appears in Collections:	[Department of Chinese Martial Arts] journal articles

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