Effect of hypoxia-inducible factor-1/vascular endothelial growth factor signaling pathway on spinal cord injury in rats

Abstract

The aim of the present study was to evaluate the expression of vascular endothelial growth factor (VEGF) and hypoxia inducible factor-1 (HIF-1), and to investigate the role of the HIF-1/VEGF signaling pathway following spinal cord injury (SCI). A total of 90 12-week-old Sprague Dawley rats were randomly divided into the following three groups: Sham group (operation without SCI); control group (SCI without ML228 treatment); and treatment group (SCI receiving ML228 treatment). ML228 was administered as it is an activator of HIF-1α. The control and treatment groups were subjected to spinal cord hemisection and motor activity was evaluated using the Basso, Beattie and Bresnahan (BBB) scoring system. Expression of HIF-1α and VEGF in each injured spinal cord section was assessed using immunohistochemistry. Prior to SCI, there were no significant differences in the BBB score among the three groups (P>0.05). However, one day after the operation, the BBB score of the sham group was significantly higher than that of the other two groups (P<0.05) and the BBB scores of the control and treatment groups did not differ significantly (P>0.05). BBB scores 3 and 7 days following surgery were significantly higher in the sham group than the other two groups (P<0.05) and the BBB scores of the treatment group were significantly higher than those of the control group (P<0.05). The expression of HIF-1α and VEGF proteins in all groups were measured 1, 3 and 7 days after the operation, and it was observed that their expression was higher in the treatment group than in the control group (P<0.05). Therefore, the results of the current study suggest that ML228 may effectively activate the HIF-1α/VEGF signaling pathway to promote the expression of HIF-1α and VEGF proteins within the injured segment of the spinal cord, which promotes neural functional recovery following SCI in rats. Therefore, treatment with ML228 may be developed as a novel therapeutic strategy to treat SCI.