Glial response and myelin clearance in areas of wallerian degeneration after spinal cord hemisection in the monkey macaca fascicularis

Abstract

Spinal cord injury (SCI) in mammals not only damages the focal area, but also leads to wallerian degeneration (WD) of axons and myelin distal to the injury. In the present study, we investigated cellular responses within areas of WD of a sensory pathway, the fasciculus gracilis, after a T8-9 lateral spinal hemisection in the adult monkey Macaca fascicularis. Spinal cord segments rostral and caudal to the injury at two clinically-relevant time points, 1 week and 4 weeks post-SCI, representing subacute and chronic stages, respectively, were examined. We observed marked axon degeneration in the areas of WD at the subacute stage, and minimal axonal neurofilament staining at the chronic stage. At the ultrastructural level, however, many degenerating axonal profiles remained at the chronic stage. Myelin breakdown was a much-delayed process. A large number of residual myelin sheaths was observed at the chronic stage. In contrast to rodents, a substantial astrogliotic response was not found in the WD regions up to 4 weeks post-injury. Microglia activation was evident in the WD areas at the subacute stage, and was enhanced at the chronic stage. However, the lack of round reactive microglia/macrophages in these regions suggests that microglial activation was either delayed or incomplete. Thus it appears that many pathological characteristics of WD in monkeys are much delayed compared to those in rodents, but are similar to those in humans. Our results suggest that non-human primate SCI models are useful for evaluating repair strategies before they are translated to clinical trials of human SCI. © 2009, Mary Ann Liebert, Inc.