Spontaneous and induced aberrant sprouting at the site of injury is irrelevant to motor function outcome in rats with spinal cord injury

Abstract

In the absence of effective regeneration following spinal cord (SC) injury, sprouting from undamaged axons has been regarded as an underlying factor for functional improvement after incomplete SC injury. The influence of spontaneous and induced axonal sprouting at the injury site on motor function was tested using rats subjected to moderate SC contusion at T9 level, using megadoses of methylprednisolone (MP) and intralesion implantation of cells from sciatic nerve (PNI). Groups using MP and PNI combined, implant vehicle, and injury with no treatment were also included. Amount of sprouting at the injury sites was significantly different depending on treatment. It was abundant in PNI-treated rats, moderate in rats treated with vehicle or nontreated, and limited in rats given MP with or without PNI (chi2, p=0.0084). This sprouting showed an aberrant course and was located in proliferating tissue at the site of injury, characterized by the presence of ependymal cells, macrophages, and myelinating and nonmyelinating Schwann cells. Functional scores and amount of spared white matter were not significantly different among groups. Correlation of the amount of sprouting vs. functional outcome or vs. amount of spared tissue was not significant, while correlation of functional outcome vs. amount of spared tissue was significant (p<0.0001). In conclusion, PNI increase aberrant sprouting at the injury site, while MP limits such sprouting, in either case without impact on motor function outcome. Missing guiding channels for sprouting axons could explain the absence of any functional improvement.