Abstract
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.
Publication types
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Research Support, N.I.H., Intramural
MeSH terms
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Animals
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Blood-Brain Barrier / drug effects*
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Blotting, Western
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Body Water / metabolism
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Brain Chemistry / drug effects
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Brain Chemistry / physiology
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Brain Edema / drug therapy
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Brain Edema / etiology
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Butyrates / pharmacology
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Coloring Agents
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Evans Blue
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Histone Deacetylase Inhibitors / therapeutic use*
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Histone Deacetylases / metabolism
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Immunoglobulin G / metabolism
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Infarction, Middle Cerebral Artery / drug therapy
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Infarction, Middle Cerebral Artery / pathology
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Ischemic Attack, Transient / drug therapy*
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Ischemic Attack, Transient / pathology*
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Male
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Matrix Metalloproteinase Inhibitors*
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NF-kappa B / biosynthesis
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NF-kappa B / genetics
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Neuroprotective Agents*
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Protease Inhibitors*
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Rats
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Rats, Sprague-Dawley
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Tight Junctions / drug effects
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Tight Junctions / pathology
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Valproic Acid / pharmacology*
Substances
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Butyrates
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Coloring Agents
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Histone Deacetylase Inhibitors
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Immunoglobulin G
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Matrix Metalloproteinase Inhibitors
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NF-kappa B
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Neuroprotective Agents
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Protease Inhibitors
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Evans Blue
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Valproic Acid
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Histone Deacetylases