HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats

HDAC inhibitor increases histone H3 acetylation and reduces microglia inflammatory response following traumatic brain injury in rats
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DOI:
10.1016/j.brainres.2008.05.085
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发表时间:
2008-08-21
期刊:
影响因子:
2.9
通讯作者:
Lyeth, Bruce G.
Lyeth, Bruce G.
中科院分区:
医学3区
文献类型:
--
作者:
Zhang, Bin;West, Eric J.;Lyeth, Bruce G.

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创伤性脑损伤(TBI)在脑中产生快速和强烈的炎症反应,其部分特征在于小胶质细胞的激活。在大鼠侧位液压冲击脑外伤后立即全身注射一种新的组蛋白去乙酰化酶(HDAC)抑制剂4-二甲氨基-N-[5-(2-巯基乙酰氨基)戊基]苯甲酰胺(DMA-PB)(0、0.25、2.5、25 mg/kg)。在损伤后24小时处理海马CA 2/3组织用于乙酰组蛋白H3免疫定位、OX-42免疫定位(用于小胶质细胞)和Fluoro-Jade B组织荧光(用于退化神经元)。与假TBI组相比,溶剂处理的TBI大鼠在同侧CA 2/3海马中表现出乙酰组蛋白H3免疫染色的显著减少(p
Traumatic brain injury (TBI) produces a rapid and robust inflammatory response in the brain characterized in part by activation of microglia. A novel histone deacetylase (HDAC) inhibitor, 4-dimethylamino-N-[5-(2-mercaptoacetylamino)pentyl]benzamide (DMA-PB), was administered (0, 0.25, 2.5, 25 mg/kg) systemically immediately after lateral fluid percussion TBI in rats. Hippocampal CA2/3 tissue was processed for acetyl-histone H3 immunolocalization, OX-42 immunolocalization (for microglia), and Fluoro-Jade B histofluorescence (for degenerating neurons) at 24 h after injury. Vehicle-treated TBI rats exhibited a significant reduction in acetyl-histone H3 immunostaining in the ipsilateral CA2/3 hippocampus compared to the sham TBI group (p