Lentivirus-mediated overexpression of netrin-1/DCC co-expression promotes axonal regeneration and functional recovery in spinal cord injury via the inhibition of the NgR1-RhoA-ROCK signaling pathway.

Abstract

Spinal cord injury (SCI) seriously affects the health of humans and quality of life, causing disabilities. Due to the ever-increasing traffic and cases of natural disasters, such as earthquakes, the incidence of SCI increases every year, thus causing a huge economic burden to society and patients. The lack of neurotrophic factors in the area affected by SCI and the presence of inhibitory factors for axonal regeneration are important reasons that make spinal cord regeneration and repair extremely difficult. Additionally, the correct projection of axons also plays an important role. As Netrin-1 is a signaling factor that guides axon growth, in this study, to determine whether Netrin-1 can promote axonal regeneration after binding to the receptor DCC following SCI, a Netrin-1/DCC co-expression recombinant lentiviral vector was constructed. This vector was used to assess the effect of Netrin-1 on the NgR1-RhoA-ROCK signaling pathway in an SCI model constructed in this study. Our results suggested that Netrin-1 exerts neuroprotective effects by inhibiting the NgR1-RhoA-ROCK signaling pathway after binding to its receptor DCC.