Considerations for Experimental Neuromodulation Following Grafting of the Spinal Cord to Skeletal Muscles for Clinical Application

Abstract

No current microsurgical approach has been clinically demonstrated to restore voluntary motor functioning distal to the site of spinal cord severance, for example, by direct reconnection of motor neurons within the cord tissue. Studies have shown that a number of different factors may account for the nonpermissiveness of the spinal cord environment and the limited functional regeneration of axons across the site of complete spinal cord damage. Building on the seminal work of David and Aguayo, Brunelli and colleagues showed that central axons are able to regenerate and extend long distances through a peripheral nerve graft, suggesting that they can regrow in an appropriate environment. However, their successfully tested and novel concept of peripheral nerve bypass grafting has not yet been implemented for further reconstructive experimental or clinical procedures for the treatment of brachial plexus or complete spinal cord injury. Their concept of central nervous system (CNS) single-cell plasticity remains a matter of ongoing debate. Neuroprotection and neuroplasticity following spinal cord injury are crucial for functional recovery and are dependent on CNS neuromodulation. Our transdisciplinary experimental study aimed to validate Brunelli’s paradigm in adult female Sprague–Dawley rats. We analyzed biochemical and histomorphological changes associated with CNS plasticity and neuromodulation to clarify the pathogenetic mechanisms underlying focal damage, as well as the interactions and overlap with neuroprotective and repair processes (i.e., endogenous defense activities). With this work, we hope to establish a robust new animal experimental paradigm that might be transferred later to clinical practice.