The Effect of Autophagy on Graded Contusive Spinal Cord Injury

Traumatic spinal cord injury (SCI) causes neuronal loss and axonal interruption. Most neurons and glial cells at the epicenter of the injury site undergo necrosis or apoptosis after injury. Autophagy, the third type of cell death, is known to eliminate the mis-folding proteins or damaged organelles, to maintain cell survival. Previous studies have showed that autophagy contributed to the inhibition of apoptosis, which exerted neuroprotective functions, not only in many neurodegenerative diseases, but also in traumatic and ischemic brain injury. By contrast, the detrimental effects of autophagy have been reported in traumatic brain injury rat model, after induction the expression of autophagic proteins. However, the relationship between autophagy and spinal cord injury is not well elucidated. The objective of this proposal is to investigate the role of autophagy in contusive SCI of different severities. Animals are employed contusive spinal cord injury with NYU impactor under 6.25 mm, and 25 mm-height level. At different recovery time (post-contusive day 0.5, 1, 3, 7, 10, 14), the spinal cords are harvested for protein analysis, immunohistochemistry, and electron microscopy. In Specific aim 1, we will investigate the expression of autophagy after graded contusive SCI at different recovery time points and at different severities. We will evaluate the autophagy-related proteins, beclin-1 and light chain 3 (LC-3), and the ultrastructures. In Specific aim 2, we will determine the role of autophagy in the functional performances at the chronic stage of graded contusive Autophagy will be modulated by either an inhibitor (3-MA) or an enhancer (rapamycin) immediately after SCI. Both motor (Basso-Beattie-Bresnahan scale) and sensory (spinal somatosensory-evoked potentials) functions will be recorded weekly for 6 weeks. The ultimate goal of this study is to characterize the role of autophagy in contusive SCI and understand the molecular basis of SCI, which can help in developing new therapies in the future.