Graduate School of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan.
Department of Rehabilitation Science, Faculty of Health Sciences, Hokkaido University, Kita 12 Nishi 5, Kita-ku, Sapporo, 060-0812, Japan.
J Stroke Cerebrovasc Dis. 2023 Sep;32(9):107275. doi: 10.1016/j.jstrokecerebrovasdis.2023.107275. Epub 2023 Jul 29.
Post-stroke cognitive impairment (PSCI) interferes with neurorehabilitation in patients with stroke. Epigenetic regulation of the hippocampus has been targeted to ameliorate cognitive function. In particular, the acetylation level of histones is modulated by exercise, a potent therapy for patients with stroke.
We examined the effects of exercise and pharmacological inhibition of histone deacetylase (HDAC) using sodium butyrate (NaB) on cognitive function and epigenetic factors in the hippocampus after intracerebral hemorrhage (ICH) to seek beneficial neuronal conditioning against PSCI. Forty rats were randomly assigned to five groups: sham, control, NaB, exercise, and NaB plus exercise groups (n=8 in each group). Except for those in the sham group, all rats underwent stereotaxic ICH surgery with a microinjection of collagenase solution. Intraperitoneal administration of NaB (300 mg/kg) and treadmill exercise (11 m/min for 30 min) were conducted for approximately 4 weeks starting 3 days post-surgery.
ICH reduced cognitive function, as detected by the object location test, accompanied by enhanced activity of HDACs. Although exercise did not modulate HDAC activity or cognitive function, repetitive NaB administration increased HDAC activity and ameliorated cognitive impairment induced by ICH.
This study suggests that pharmacological treatment with an HDAC inhibitor could potentially present an enriched epigenetic platform in the hippocampus and ameliorate PSCI for neurorehabilitation following ICH.
脑卒中后认知障碍（PSCI）会干扰脑卒中患者的神经康复。海马体的表观遗传调控已被作为改善认知功能的靶点。特别是，组蛋白的乙酰化水平可通过运动来调节，运动是脑卒中患者的一种有效治疗方法。
我们研究了运动和使用组蛋白去乙酰化酶（HDAC）抑制剂丁酸钠（NaB）对脑出血（ICH）后海马体认知功能和表观遗传因素的影响，以寻求对 PSCI 有益的神经元调节作用。40 只大鼠被随机分为 5 组：假手术组、对照组、NaB 组、运动组和 NaB 加运动组（每组 8 只）。除假手术组外，所有大鼠均接受立体定向 ICH 手术，脑内注射胶原酶溶液。ICH 手术后 3 天开始，腹腔内给予 NaB（300mg/kg）和跑步机运动（11m/min，30min），持续约 4 周。
ICH 降低了大鼠的认知功能，表现在物体位置测试中，同时伴有 HDACs 活性增强。虽然运动并没有调节 HDAC 活性或认知功能，但重复给予 NaB 可增加 HDAC 活性，并改善 ICH 引起的认知障碍。
本研究表明，HDAC 抑制剂的药物治疗可能为海马体提供丰富的表观遗传平台，并改善 ICH 后神经康复的 PSCI。
