| Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition. | |
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MedLine Citation:
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PMID: 20978517 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Valproic acid (VPA), a histone deacetylase (HDAC) inhibitor, is known to protect against cerebral ischemia. The effects of VPA on blood-brain barrier (BBB) disruption were investigated in rats subjected to transient middle cerebral artery occlusion (MCAO). Postischemic VPA treatment remarkably attenuated MCAO-induced BBB disruption and brain edema. Meanwhile, VPA significantly reduced MCAO-induced elevation of matrix metalloproteinase-9 (MMP-9), degradation of tight junction proteins, and nuclear translocation of nuclear factor-κB (NF-κB). Sodium butyrate, another HDAC inhibitor, mimicked these effects of VPA. Our findings suggest that BBB protection by VPA involves HDAC inhibition-mediated suppression of NF-κB activation, MMP-9 induction, and tight junction degradation. |
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Authors:
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Zhifei Wang; Yan Leng; Li-Kai Tsai; Peter Leeds; De-Maw Chuang |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Intramural Date: 2010-10-27 |
Journal Detail:
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Title: Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism Volume: 31 ISSN: 1559-7016 ISO Abbreviation: J. Cereb. Blood Flow Metab. Publication Date: 2011 Jan |
Date Detail:
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Created Date: 2011-01-04 Completed Date: 2011-02-03 Revised Date: 2012-01-02 |
Medline Journal Info:
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Nlm Unique ID: 8112566 Medline TA: J Cereb Blood Flow Metab Country: United States |
Other Details:
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Languages: eng Pagination: 52-7 Citation Subset: IM |
Affiliation:
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Molecular Neurobiology Section, National Institute of Mental Health, National Institutes of Health, Bethesda, Maryland 20892-1363, USA. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Blood-Brain Barrier / drug effects* Blotting, Western Body Water / metabolism Brain Chemistry / drug effects, physiology Brain Edema / drug therapy, etiology Butyrates / pharmacology Coloring Agents Evans Blue Histone Deacetylase Inhibitors / therapeutic use* Histone Deacetylases / metabolism Immunoglobulin G / metabolism Infarction, Middle Cerebral Artery / drug therapy, pathology Ischemic Attack, Transient / drug therapy*, pathology* Male Matrix Metalloproteinase 9 / antagonists & inhibitors* NF-kappa B / biosynthesis, genetics Neuroprotective Agents* Protease Inhibitors* Rats Rats, Sprague-Dawley Tight Junctions / drug effects, pathology Valproic Acid / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Butyrates; 0/Coloring Agents; 0/Histone Deacetylase Inhibitors; 0/Immunoglobulin G; 0/NF-kappa B; 0/Neuroprotective Agents; 0/Protease Inhibitors; 314-13-6/Evans Blue; 99-66-1/Valproic Acid; EC 3.4.24.35/Matrix Metalloproteinase 9; EC 3.5.1.98/Histone Deacetylases |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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