Stabilization of HIF-1α by DMOG promotes the recovery of acute spinal cord injury by inhibiting neural apoptosis and enhancing axon regeneration.

Abstract

Spinal cord injury (SCI) is a devastating neurological disorder that usually leads to loss of motor and sensory of the victims. The expression of hypoxia inducible factor-1α (HIF-1α) is increased and exerts a protective role after traumatic SCI. However, the endogenous activity of HIF-1α is insufficient for promoting function recovery. The present study tested the potential effect of sustained activation of HIF-1α by the prolylhydroxylase (PHD) inhibitor dimethyloxaloylglycine (DMOG) on anti-apoptosis and regulating axonal regeneration after SCI. Here, we found that treatment with DMOG significantly increases the expression of HIF-1α, the stabilization of HIF-1α induced by DMOG not only decreases the expressions of apoptotic proteins for neurons survival, but also enhances the axonal regeneration through regulating microtubule stabilization in vivo and vitro. In addition, we found that DMOG promotes neurons survival and axonal regeneration through activating autophagy induced by HIF-1α/BNIP3 signaling pathway, and inhibition of HIF-1α or autophagy abrogates the protective of DMOG as expected. Taken together, our study demonstrated that treatment with DMOG improves functional recovery after SCI, and DMOG may serve as a potentially applicable candidate for treating SCI.