TY - JOUR
T1 - Entinostat improves acute neurological outcomes and attenuates hematoma volume after Intracerebral Hemorrhage
AU - Bonsack, Frederick
AU - Sukumari-Ramesh, Sangeetha
N1 - Funding Information:
This work was supported by grants from the National Institutes of Health (R01NS107853) and American Heart Association (14SDG18730034) to SSR.
Publisher Copyright:
© 2020 Elsevier B.V.
PY - 2021/2/1
Y1 - 2021/2/1
N2 - 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.
AB - 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.
KW - Entinostat
KW - Epigenetics
KW - ICH
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U2 - 10.1016/j.brainres.2020.147222
DO - 10.1016/j.brainres.2020.147222
M3 - Article
C2 - 33358731
AN - SCOPUS:85098950427
SN - 0006-8993
VL - 1752
JO - Brain Research
JF - Brain Research
M1 - 147222
ER -
