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

Bin Zhang, Eric J. West, Ken C. Van, Gene G Gurkoff, Jia Zhou, Xiu Mei Zhang, Alan P. Kozikowski, Bruce G Lyeth

Research output: Contribution to journalArticle

94 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)181-191
Number of pages11
JournalBrain Research
Volume1226
DOIs
StatePublished - Aug 21 2008

Keywords

  • Fluid percussion
  • Histone deacetylase
  • Inflammation
  • Microglia
  • Traumatic brain injury

ASJC Scopus subject areas

  • Neuroscience(all)
  • Clinical Neurology
  • Developmental Biology
  • Molecular Biology

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