Evaluation of histone deacetylases inhibition in the neuronal death spread and in the function recovery after spinal cord transection in rats

Abstract

The spinal cord could be damaged front many different situations as transportation accident, falls and fights with weapons and knives leading to paraplegic or tetraplegic state, very disability conditions that has been considered for medicine researchers. Studies suggest that paraplegic and tetraplegic people, beyond disability to walk with their own legs, suffer with increased chances of urinary tract inflammation, fractures, thrombosis, cardiovascular problems, tumor and depression. After the initial injury, the inflammatory system is highly activated, exacerbating the lesion effects. Many processes related to chromatin modifications (epigenetic) have been identified in spread of injury's secondary effects. Apparently, the inhibition of histone deacetylases could decrease inflammation, it could help the motor function recovery and axonal regeneration after spinal cord injury. However yet there are no much knowledge in the field of epigenetic and Policomb enzyme inhibition, genes that act in genic transcription repressors. Therefore, the aim of this project is to evaluate the neuronal damage, axonal regeneration and motor function recovery of Wistar rats, submitted to spinal cord transection and pharmacological treatment with Valproic acid and EZH2 inhibitor directly in the lesion site. After spinal cord injury and pharmacological treatment, motor and sensorial function recovery will be accessed by footprint analyses, open field measures and rotarod test after 1, 7 and 14 days. Animals with 1, 7 and 14 days after spinal cord injury will have head decapitation after anesthesia, a spinal cord segment will be dissected for molecular experiments as TUNEL assay, immunofluorescence, real time PCR for Policomb gene and protein description (SUZ12 and EZH2) and secondary cellular death spread analyses.