Background
Deficient DNA repair and excessive DNA damage contribute to neurodegenerative disease. However, the role of DNA damage and repair in spinal cord injury (SCI) is unclear. SCI, a debilitating disruption of the structural and biological network of the spinal cord, is characterized by oxidative stress. Nevertheless, the pathophysiological mechanisms leading to neuronal loss following SCI remain incompletely defined.
Conclusion
Our study indicates a possible role of DNA damage in neuronal loss following SCI and highlights the need for early interventions targeting DNA repair to preserve neuronal tissue.
Methods
Using a contusion model, a severe SCI was induced at the L1 spinal level in C57Bl/6J mice. The temporal and spatial presence of DNA damage was then determined via immunolabeling for the DNA damage marker, γH2AX, from 1 h post-injury (hpi) to 28 days post-injury (dpi).
Results
Our analysis revealed that increased DNA damage foci were present from 1 hpi to 3 dpi in SCI mice relative to controls (sham surgery and naive), with the damage signal spreading over time longitudinally from the affected area to more rostral and caudal regions. Co-labeling of γH2AX with NeuN revealed neuronal specificity of DNA damage, with increased early cell death (pan-nuclear γH2AX) peaking at 1 dpi and apoptosis (cleaved Caspase-3) arising later at 3 dpi.