Matrix metalloproteinase-9 regulates the blood brain barrier via the hedgehog pathway in a rat model of traumatic brain injury

Abstract

The mechanisms of secondary brain injury after traumatic brain injury (TBI) are complex and are the result of multiple factors. Protecting the blood-brain barrier (BBB) and ameliorating cerebral edema are two key factors for improving the prognosis of TBI patients. The BBB is regulated by the hedgehog pathway through Scube2 and Shh protein. Matrix metalloproteinase-9 (MMP-9) influences the transport system and enzyme system of vascular endothelial cells, possibly via the hedgehog pathway. The present study aimed to investigate the role and mechanism of MMP-9 in TBI via the hedgehog pathway. Eighty male Sprague-Dawley rats were used to establish a murine model of TBI. Subsequently, the effect of SB-3CT—a specific inhibitor of MMP-9—was assessed via Western blotting, real-time PCR, immunofluorescence, apoptotic assays, and neurological scoring. The results showed that, compared with those of the sham-operation group, the mRNA and protein levels of MMP-9 were significantly increased after TBI, while the expressions of Scube2 and Shh were decreased. Application of SB-3CT at 24 h after TBI significantly reduced neuronal apoptosis and BBB permeability, while increasing expressions of Scube2 and Shh. In conclusion, these findings demonstrate an influence of TBI-induced MMP-9 upregulation in the induction of post-traumatic nerve and BBB injury, which may be partially mediated by Scube2 and Shh via the hedgehog pathway.