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.
['Abdanipour|Alireza|A|', 'Schluesener|Hermann J|HJ|', 'Tiraihi|Taki|T|']
D000818:Animals D019208:Brain-Derived Neurotrophic Factor D003288:Contusions D016207:Cytokines D053331:Ectodysplasins D044127:Epigenesis, Genetic D005260:Female D051100:Glial Cell Line-Derived Neurotrophic Factor D056572:Histone Deacetylase Inhibitors D007796:Laminectomy D008264:Macrophages D017628:Microglia D008869:Microtubule-Associated Proteins D009043:Motor Activity D018696:Neuroprotective Agents D012333:RNA, Messenger D011897:Random Allocation D051381:Rats D017207:Rats, Sprague-Dawley D020127:Recovery of Function D013116:Spinal Cord D013119:Spinal Cord Injuries D014635:Valproic Acid
Valproic acid Epigenetics Inflammation