The correlation between hypoxia-inducible factor-1α, matrix metalloproteinase-9 and functional recovery following chronic spinal cord compression

Abstract

The molecular mechanisms underlying cervical spondylotic myelopathy (CSM) are poorly understood. To assess the correlation between HIF-1α, MMP-9 and functional recovery following chronic cervical spinal cord compression (CSCI). Rats in the sham group underwent C5 semi-laminectomy, while a water-absorbable polyurethane polymer was implanted into the C6 epidural space in the chronic CSCI group. Basso, Beattie and Bresnahan score and somatosensory evoked potentials were used to evaluate neurological function. Hematoxylin and eosin staining was performed to assess pathological changes in the spinal cord, while immunohistochemical analysis was used to examine HIF-1α and MMP-9 expression on days 7, 28, 42 and 70 post-surgery. Normal rats were only used for HE staining. The BBB score was significantly reduced on day 28 following CSCI, while SEPs exhibited decreased amplitude and increased latency. In chronic CSCI group, the BBB score and SEPs significantly improved on day 70 compared with day 28. HE staining revealed different level of spinal cord edema after chronic CSCI. Compared with the sham group, immunohistochemical analyses revealed that HIF-1α- and MMP-9-positive cells were increased on day 7 and peaked on day 28. HIF-1α and MMP-9 expression were demonstrated to be significantly positively correlated, whereas HIF-1α expression and BBB score were significantly negatively correlated, as well MMP-9 expression and BBB score. HIF-1α and MMP-9 expression are increased following chronic spinal cord compression and are positively correlated with one another. Decreased expression of HIF-1α and MMP-9 may contribute to functional recovery following CSCI. This expression pattern of HIF-1α and MMP-9 may give a new perspective on the molecular mechanisms of CSM.