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

被引：115

作者：

Zhang, Bin ^{[1
,2
]}

West, Eric J. ^{[1
]}

Van, Ken C. ^{[1
]}

Gurkoff, Gene G. ^{[1
]}

Zhou, Jia ^{[4
]}

Zhang, Xiu-Mei ^{[2
]}

Kozikowski, Alan P. ^{[3
]}

Lyeth, Bruce G. ^{[1
]}

机构：

[1] Univ Calif Davis, Dept Neurol Surg, Davis, CA 95616 USA

[2] Shandong Univ, Sch Med, Dept Pharmacol, Jinan 250012, Shandong, Peoples R China

[3] Univ Illinois, Drug Discovery Program, Dept Med Chem & Pharmacognosy, Chicago, IL 60612 USA

[4] PsychoGen Inc, Tarrytown, NY 10591 USA

来源：

BRAIN RESEARCH | 2008年 / 1226卷

关键词：

traumatic brain injury; microglia; inflammation; histone deacetylase; fluid percussion;

D O I：

10.1016/j.brainres.2008.05.085

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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<0.05). The reduction in acetyl-histone H3 immunostaining was attenuated by each of the DMA-PB dosage treatment groups. Vehicle-treated TBI rats exhibited a high density of phagocytic microglia in the ipsilateral CA2/3 hippocampus compared to sham TBI in which none were observed. All doses of DMA-PB significantly reduced the density of phagocytic microglia (P<0.05). There was a trend for DMA-PB to reduce the number of degenerating neurons in the ipsilateral CA2/3 hippocampus (p = 0.076). We conclude that the HDAC inhibitor DMA-PB is a potential novel therapeutic for inhibiting neuroinflammation associated with TBI. (C) 2008 Elsevier B.V. All rights reserved.

引用

页码：181 / 191

页数：11

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