The cauda equina is formed from collection of ventral and dorsal nerve roots arising from the caudal end of the spinal cord. Approximately 15-30% of traumatic injuries to the spine occur at or below the thoracolumbar junction. As a result, about 40,000 Americans currently suffer from the debilitating effects of cauda equina injury. Goal. This study's ultimate goal is to identify and repair injured ventral roots in a rat model as proof-of-concept that similar techniques could feasibly be used in human patients, for which no treatments exist. This potential translational application forms the foundation for this study, and as such, all techniques adhere to clinically practical constraints. Injury model and outcomes. To achieve these ends, a novel injury model has been developed in the rat where ventral roots are identified by way of electrophysiological mapping of each root's innervation pattern. Following excision of short segments from these roots, injured controls will be rigorously characterized by way of functional and behavioral outcomes over a 26-week span, at which point anatomical measures of regeneration will be analyzed. Regeneration in repaired animals will be assessed in the same manner. Repair with Schwann cells. Given their documented regenerative effect in peripheral nerve repair, Schwann cells were identified as ideal candidates for intervention following ventral root injury. Improved functional outcome is the primary outcome measure of interest, though this study compares treatment with Schwann cells harvested from different sites, as we hypothesize that those harvested from ventral roots (predominantly motor phenotype) will show superior regenerative effect compared to those harvested from dorsal roots (predominantly sensory phenotype) or sciatic nerves (mixed phenotypes). As a precursor to the functional outcomes measured in vivo, a series of in vitro experiments will measure growth factor expression by way of multiplex protein capture and delineate the regenerative potency of each cell group through co-culture with motor or sensory neurons. It is hypothesized that such differences will inform Schwann cell harvesting practices in the future, ideally through modality-like expansion of cells taken from tissue at the injury site proper.
Cauda equina injury is associated with debilitating consequences for patients, and it is unfortunately common following traumatic injury to the spine. However, no good injury models exist, and current treatments are severely lacking. This research aims to 1) repair cauda equina ventral roots in a novel injury model using Schwann cells and 2) establish the ideal Schwann cell phenotype for doing so.
|Mackenzie, Samuel J; Yi, Juneyoung L; Singla, Amit et al. (2018) Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam. Muscle Nerve 57:E78-E84|
|MacKenzie, Samuel J; Yi, Juneyoung L; Singla, Amit et al. (2015) Innervation and function of rat tail muscles for modeling cauda equina injury and repair. Muscle Nerve 52:94-102|