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

被引：7

作者：

Bonsack, Frederick ^{[1
]}

Sukumari-Ramesh, Sangeetha ^{[1
]}

机构：

[1] Augusta Univ, Med Coll Georgia, Dept Pharmacol & Toxicol, 1120 15th St,CB3618, Augusta, GA 30912 USA

来源：

BRAIN RESEARCH | 2021年 / 1752卷

基金：

美国国家卫生研究院;

关键词：

ICH; Epigenetics; Entinostat; HISTONE DEACETYLASE INHIBITOR; ACUTE INFLAMMATORY REACTION; HDAC INHIBITORS; CELL-DEATH; KAPPA-B; ACETYLATION; MS-275; NEUROPROTECTION; DIFFERENTIATION; MECHANISMS;

D O I：

10.1016/j.brainres.2020.147222

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

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.

引用

页数：8