Neuroprotective Effects of Valproic Acid in a Rat Model of Cauda Equina Injury

BACKGROUND: Histone deacetylase inhibitors, including valproic acid (VPA), are promising therapeutic interventions in neurological disorders and play an important role in synaptic activity and neuronal function. METHODS: A total of 30 rats were randomly allocated to 3 groups: sham, control, and VPA. The rats in the VPA and control groups received laminectomy at the L4 level of the vertebrae and silicone gel implantation into the epidural spaces L5 and L6. Rats in the sham group only received laminectomy at the L4 level of vertebrae without any implantation. VPA (300 mg/kg in saline) was administered 2 hours before the surgery. After the surgery, the VPA group received further VPA injections at 300 mg/kg twice a day for 1 week. The same volume of saline was injected in the control group. Neurobehavioral tests using the Basso, Beattie, Bresnahan scale and the oblique board test were performed for 1 week starting at 2 hours before surgery up to day 7 after surgery. At day 7 after surgery, tissues from the compressed cauda equina (L5-L6) were subjected to hematoxylin and eosin, luxol fast blue, or immunofluorescence staining, whereas the terminal deoxynucleotidyl transferase-mediated biotinylated UTP nick-end label assay staining was performed on the tissue from the dorsal root ganglions and the lumbar segment of the spinal cord proximal to the compressed cauda equina (L5-L6). RESULTS: The behavioral results suggested a significant improvement in the lower limb motor function in the VPA group compared with controls (P < 0.05). Furthermore, histologic assessment revealed a significant reduction in nerve fibers showing Wallerian degeneration and demyelinating lesions in the VPA group, in addition to an increased myelination compared with the control group (P < 0.05). The terminal deoxynucleotidyl transferasemediated biotinylated UTP nick-end label assay staining revealed a significant decrease in the number of apoptotic neurons in the spinal cord anterior horn and dorsal root ganglions in the VPA group compared with controls (P < 0.05). CONCLUSIONS: Our data demonstrated that VPA could alleviate cauda equina injury, reduce apoptotic cells, and improve motor recovery, suggesting a neuroprotective effect in acute cauda equina syndrome.