Valproic Acid Ameliorates Locomotor Function in the Rat Model of Contusion via Alteration of Mst1, Bcl-2, and Nrf2 Gene Expression

Background: As a novel pro-apoptotic kinase, Mammalian sterile 20–like kinase 1 (Mst1) promotes programmed cell death in animal models of inflammatory diseases. This research aimed to determine the level of expression of Mst1 gene in a rat model of spinal cord injury (SCI) treated with valproic acid (VPA). Methods: Animals were divided into four groups: Contused animals (untreated); laminectomy (control); contused animals treated with normal saline (0.5 ml) (vehicle) and treated with VPA (Sigma, USA; 400 mg / kg) (treatment). BBB (Basso, Beattie, Bresnahan) locomotor scale method was performed once a week for four weeks to determine locomotor function following SCI. On the 28th day post-SCI, rats were sacrificed and the spinal cord lesion region was removed. H&E staining and TUNEL assay were performed to detect cavity formation and apoptosis in the spinal cord, respectively. The mRNA levels of the genes Mst1, Nrf2 and Bcl-2 were evaluated using quantitative real-time PCR. Results: The results of real-time PCR showed that expression of Mst1 genes was significantly reduced in VPA treated group relative to untreated group. Histological assessment revealed that VPA injection significantly reduced the number of TUNEL-positive cells as well as the cavity volume. The findings also showed significant improvement of the motor function in the VPA group treated compared to the untreated group (P≤0.05). Conclusion: Our findings indicate that, Valproic acid-mediated neuroprotection in SCI injuries may in part be due to decreasing expression of pro-apoptotic genes such as Mst1.