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 HDAC inhibitor, 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 class1 histone deacetylase inhibitor, Entinostat, in improving acute neurological function after ICH warranting further investigation.

脑出血 (ICH) 或出血性中风是一个重大的公共卫生问题，目前尚无有效的治疗方法。鉴于表观遗传机制在 ICH 病理生理学中的新兴作用，我们检验了 1 类 HDAC 抑制剂 Entinostat 减轻 ICH 后神经退行性变并改善神经行为结果的假设。为了解决这个问题，我们采用了 ICH 的临床前小鼠模型，并且在 ICH 诱导后一小时腹膜内给予 Entinostat。与载体处理的对照相比，Entinostat 处理显着减少了 ICH 后退化神经元和 TUNEL 阳性细胞的数量。此外，Entinostat 治疗显着减少了血肿体积、T2 加权出血病灶体积并改善了 ICH 后的急性神经系统预后。更远，Entinostat 在体外显着降低了血红素诱导的促炎细胞因子的释放。与对照组相比，在 ICH 后 Entinostat 治疗组中促炎性小胶质细胞/巨噬细胞标志物 CD16/32 的表达显着降低。总之，数据表明 1 类组蛋白去乙酰化酶抑制剂 Entinostat 在 ICH 后改善急性神经功能方面的潜力值得进一步研究。