Entinostat improves acute neurological outcomes and attenuates hematoma volume after Intracerebral Hemorrhage

Frederick Bonsack, Sangeetha Sukumari-Ramesh

Research output: Contribution to journalArticlepeer-review

Abstract

Intracerebral hemorrhage (ICH) or hemorrhagic stroke is a major public health problem with no effective treatment. Given the emerging role of epigenetic mechanisms in the pathophysiology of ICH, we tested the hypothesis that a class 1 histone deacetylase inhibitor (HDACi), Entinostat, attenuates neurodegeneration and improves neurobehavioral outcomes after ICH. To address this, we employed a preclinical mouse model of ICH and Entinostat was administered intraperitoneally one-hour post induction of ICH. Entinostat treatment significantly reduced the number of degenerating neurons and TUNEL-positive cells after ICH in comparison to vehicle-treated controls. Moreover, Entinostat treatment significantly reduced hematoma volume, T2-weighted hemorrhagic lesion volume and improved acute neurological outcomes after ICH. Further, Entinostat significantly reduced the hemin-induced release of proinflammatory cytokines in vitro. Consistently, the expression of proinflammatory microglial/macrophage marker, CD16/32, was remarkably reduced in Entinostat treated group after ICH in comparison to control. Altogether, data implicates the potential of class 1 HDACi, Entinostat, in improving acute neurological function after ICH warranting further investigation.

Original languageEnglish (US)
Article number147222
JournalBrain Research
Volume1752
DOIs
StatePublished - Feb 1 2021

Keywords

  • Entinostat
  • Epigenetics
  • ICH

ASJC Scopus subject areas

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

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