Long-term effects of a lumbosacral ventral root avulsion injury on axotomized motor neurons and avulsed ventral roots in a non-human primate model of cauda equina injury

Abstract

Here, we have translated from the rat to the non-human primate a unilateral lumbosacral injury as a model for cauda equina injury. In this morphological study, we have investigated retrograde effects of a unilateral L6–S2 ventral root avulsion (VRA) injury as well as the long-term effects of Wallerian degeneration on avulsed ventral roots at 6–10months post-operatively in four adult male rhesus monkeys.Immunohistochemistry for choline acetyl transferase and glial fibrillary acidic protein demonstrated a significant loss of the majority of the axotomized motoneurons in the affected L6–S2 segments and signs of an associated astrocytic glial response within the ventral horn of the L6 and S1 spinal cord segments. Quantitative analysis of the avulsed ventral roots showed that they exhibited normal size and were populated by a normal number of myelinated axons. However, the myelinated axons in the avulsed ventral roots were markedly smaller in caliber compared to the fibers of the intact contralateral ventral roots, which served as controls. Ultrastructural studies confirmed the presence of small myelinated axons and a population of unmyelinated axons within the avulsed roots. In addition, collagen fibers were readily identified within the endoneurium of the avulsed roots.In summary, a lumbosacral VRA injury resulted in retrograde motoneuron loss and astrocytic glial activation in the ventral horn. Surprisingly, the Wallerian degeneration of motor axons in the avulsed ventral roots was followed by a repopulation of the avulsed roots by small myelinated and unmyelinated fibers. We speculate that the small axons may represent sprouting or axonal regeneration by primary afferents or autonomic fibers.