PMID- 24936215
OWN - NLM
STAT- PubMed-not-MEDLINE
DCOM- 20140617
LR  - 20211021
IS  - 1943-8141 (Print)
IS  - 1943-8141 (Electronic)
IS  - 1943-8141 (Linking)
VI  - 6
IP  - 3
DP  - 2014
TI  - HDAC inhibitors mitigate ischemia-induced oligodendrocyte damage: potential roles 
      of oligodendrogenesis, VEGF, and anti-inflammation.
PG  - 206-23
AB  - White matter injury is an important component of stroke pathology, but its 
      pathophysiology and potential treatment remain relatively elusive and 
      underexplored. We previously reported that after permanent middle cerebral artery 
      occlusion (pMCAO), sodium butyrate (SB) and trichostatin A (TSA) induced 
      neurogenesis via histone deacetylase (HDAC) inhibition in multiple ischemic brain 
      regions in rats; these effects-which depended on activation of brain-derived 
      neurotrophic factor (BDNF)-TrkB signaling-contributed to behavioral improvement. 
      The present study found that SB or TSA robustly protected against 
      ischemia-induced loss of oligodendrocytes detected by confocal microscopy of 
      myelin basic protein (MBP) immunostaining in the ipsilateral subventricular zone 
      (SVZ), striatum, corpus callosum, and frontal cortex seven days post-pMCAO. 
      Co-localization of 5-bromo-2'-deoxyuridine (BrdU)(+) and MBP(+) cells after SB 
      treatment suggested the occurrence of oligodendrogenesis. SB also strongly 
      upregulated vascular endothelial growth factor (VEGF), which plays a major role 
      in neurogenesis, angiogenesis, and functional recovery after stroke. These 
      SB-induced effects were markedly suppressed by blocking the TrkB signaling 
      pathway with K252a. pMCAO-induced activation of microglia (OX42(+)) and 
      macrophages/monocytes (ED1(+))-which has been linked to white matter injury-was 
      robustly suppressed by SB in a K252a-sensitive manner. In addition, SB treatment 
      largely blocked caspase-3(+) and OX42(+) cells in ipsilateral brain regions. Our 
      results suggest that HDAC inhibitor-mediated protection against ischemia-induced 
      oligodendrocyte loss may involve multiple mechanisms including 
      oligodendrogenesis, VEGF upregulation, anti-inflammation, and caspase-3 
      downregulation. Taken together, the results suggest that post-insult treatment 
      with HDAC inhibitors is a rational strategy to mitigate white matter injury 
      following ischemic stroke.
FAU - Kim, Hyeon Ju
AU  - Kim HJ
AD  - Molecular Neurobiology Section, National Institute of Mental Health, National 
      Institutes of Health Bethesda, MD 20892-1363, USA.
FAU - Chuang, De-Maw
AU  - Chuang DM
AD  - Molecular Neurobiology Section, National Institute of Mental Health, National 
      Institutes of Health Bethesda, MD 20892-1363, USA.
LA  - eng
PT  - Journal Article
DEP - 20140515
PL  - United States
TA  - Am J Transl Res
JT  - American journal of translational research
JID - 101493030
PMC - PMC4058304
OTO - NOTNLM
OT  - Anti-inflammation
OT  - HDAC inhibitors
OT  - cerebral ischemia
OT  - myelin basic protein (MBP)
OT  - oligodendrocytes
OT  - vascular endothelial growth factor (VEGF)
EDAT- 2014/06/18 06:00
MHDA- 2014/06/18 06:01
PMCR- 2014/05/15
CRDT- 2014/06/18 06:00
PHST- 2014/03/21 00:00 [received]
PHST- 2014/04/18 00:00 [accepted]
PHST- 2014/06/18 06:00 [entrez]
PHST- 2014/06/18 06:00 [pubmed]
PHST- 2014/06/18 06:01 [medline]
PHST- 2014/05/15 00:00 [pmc-release]
PST - epublish
SO  - Am J Transl Res. 2014 May 15;6(3):206-23. eCollection 2014.