effects of valproic acid, a histone deacetylase inhibitor, on improvement of locomotor function in rat spinal cord injury based on epigenetic science

background: the primary phase of traumatic spinal cord injury (sci) starts by a complex local inflammatory reaction such as secretion of pro-inflammatory cytokines from microglia and injured cells that substantially contribute to exacerbating pathogenic events in secondary phase. valproic acid (vpa) is a histone deacetylase inhibitor. acetylation of histones is critical to cellular inflammatory and repair processes. methods: in this study, rats were randomly assigned to five experimental groups (laminectomy, untreated, and three vpa-treated groups). for sci, severe contusion was used. in treated groups, vpa was administered intraperitoneally at doses of 100, 200 and 400 mg/kg daily three hours after injury for 7 days. to compare locomotor improvement among experimental groups, behavioral assessments were performed by the basso, beattie and bresnahan (bbb) rating scale. the expression of neurotrophins was evaluated by rt-pcr and real-time pcr. results: vpa administration increased regional brain-derived neurotrophic factor and glial cell-derived neurotrophic factor mrna levels. local inflammation and the expression of the lysosomal marker ed1 by activated macrophages/microglial cells were reduced by vpa and immunoreactivity of acetylated histone and microtubule-associated protein were increased. conclusion: the results showed a reduction in the development of secondary damage in rat spinal cord trauma with an improvement in the open field test (bbb scale) with rapid recovery.