Valproic acid attenuates blood-brain barrier disruption in a rat model of transient focal cerebral ischemia: the roles of HDAC and MMP-9 inhibition
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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DOI：
10.1038/jcbfm.2010.195
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发表时间：
2011-01-01
影响因子：
6.3
通讯作者：
Chuang, De-Maw
中科院分区：
文献类型：
--
作者：
Wang, Zhifei;Leng, Yan;Chuang, De-Maw
丙戊酸 (VPA) 是一种组蛋白脱乙酰酶 (HDAC) 抑制剂，已知可预防脑缺血。在短暂大脑中动脉闭塞 (MCAO) 的大鼠中研究了 VPA 对血脑屏障 (BBB) 破坏的影响。缺血后 VPA 治疗显着减轻了 MCAO 引起的 BBB 破坏和脑水肿。同时，VPA 显着降低 MCAO 诱导的基质金属蛋白酶 9 (MMP-9) 升高、紧密连接蛋白降解和核因子 kappa B (NF-kappa B) 核转位。另一种 HDAC 抑制剂丁酸钠模仿了 VPA 的这些作用。我们的研究结果表明，VPA 对 BBB 的保护涉及 HDAC 抑制介导的 NF-κ B 激活抑制、MMP-9 诱导和紧密连接降解。脑血流与代谢杂志 (2011) 31, 52-57; doi：10.1038/jcbfm.2010.195； 2010 年 10 月 27 日在线发布
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-kappa B (NF-kappa B). 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-kappa B activation, MMP-9 induction, and tight junction degradation. Journal of Cerebral Blood Flow & Metabolism (2011) 31, 52-57; doi:10.1038/jcbfm.2010.195; published online 27 October 2010