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

Biochemical Pharmacology
Chang-Ming ChernYuh-Chiang Shen

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 μg/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-κB). All of these pathological changes were diminished by 2-MS; 2-MS also intensively limited cortical infarction and promoted upexpression of neurodevelopmental genes near peri-infarct cortex and endogenous neurogenesis near subgranular zone of hippocampal dentate gyrus and the subventricular zone, most possibly by inactivat...Continue Reading

References

Jun 16, 1997·The Journal of Cell Biology·A SakakibaraS Tsukita
Jul 21, 1999·Proceedings of the National Academy of Sciences of the United States of America·E Chalecka-Franaszek, D M Chuang
Jan 4, 2003·Nature Reviews. Neuroscience·Robert M Sapolsky
Aug 3, 2004·The Journal of Clinical Investigation·Akihiko TaguchiTomohiro Matsuyama
Oct 1, 2004·Journal of Molecular Neuroscience : MN·Noa KirshenboimHagit Eldar-Finkelman
May 3, 2007·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Zhen ZhengMidori A Yenari
Dec 14, 2007·Molecular and Cellular Neurosciences·Min-Huei LiangDe-Maw Chuang
Apr 3, 2008·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hyung-Hwan KimJames K Liao
May 1, 2008·The European Journal of Neuroscience·Sandrine Willaime-Morawek, Derek van der Kooy
Apr 14, 2010·Proceedings of the National Academy of Sciences of the United States of America·Kunlin JinDavid A Greenberg
Dec 17, 2010·Expert Opinion on Investigational Drugs·Paul A Lapchak
Dec 17, 2010·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Parizad M BilimoriaAzad Bonni
Dec 29, 2010·Cell Research·Michael J Morgan, Zheng-gang Liu
May 19, 2011·Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism·Hongfu LiChanglian Zhu
Jul 16, 2011·Stroke; a Journal of Cerebral Circulation·Olle Lindvall, Zaal Kokaia
May 12, 2012·Current Pharmaceutical Design·Cesar V BorlonganDavid C Hess
Jul 13, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·David Fernández-LópezZinaida S Vexler

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Citations

Oct 14, 2014·Journal of Stroke and Cerebrovascular Diseases : the Official Journal of National Stroke Association·Jia LiuZhi Song
Jun 13, 2015·Pharmacological Research : the Official Journal of the Italian Pharmacological Society·Liang KongZhe-Yu Chen
May 6, 2016·Neuroscience Bulletin·Fengyun ZhangDongya Zhu
Oct 6, 2016·Evidence-based Complementary and Alternative Medicine : ECAM·Chin-Yi Cheng, Yu-Chen Lee

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