Epigenetic modifications in the motor cortex caused by exercise or pharmacological inhibition of histone deacetylases (HDACs) after intracerebral hemorrhage (ICH).

Epigenetic regulation is expected to provide an enriched platform for neurorehabilitation of post-stroke patients. Acetylation of specific lysine residues in histones is a potent epigenetic target essential for transcriptional regulation. Exercise modulates histone acetylation and gene expression in neuroplasticity in the brain. This study sought to examine the effect of epigenetic treatment using a histone deacetylase (HDAC) inhibitor, sodium butyrate (NaB), and exercise on epigenetic markers in the bilateral motor cortex after intracerebral hemorrhage (ICH) to identify a more enriched neuronal condition for neurorehabilitation. Forty-one male Wistar rats were randomly divided into five groups: sham (n = 8), control (n = 9), NaB, exercise (n = 8), and NaB and exercise (n = 8). Intraperitoneal administration of an HDAC inhibitor (300 mg/kg NaB) and treadmill exercise (11 m/min for 30 min) was conducted five days a week for approximately-four weeks. ICH specifically decreased the acetylation level of histone H4 in the ipsilateral cortex, and HDAC inhibition with NaB increased the acetylation level of histone H4 over the sham level, accompanied by an improvement in motor function as assessed by the cylinder test. Exercise increased the acetylation levels of histones (H3 and H4) in the bilateral cortex. Synergistic effects of exercise and NaB were not observed during histone acetylation. Pharmacological treatment with a HDAC inhibitor and exercise can provide an enriched epigenetic platform for neurorehabilitation in an individual manner.