Regeneration of acutely and chronically injured descending respiratory pathways within post-traumatic nerve grafts

Abstract

Central respiratory neurons, which are acutely axotomized by peripheral nerve grafts implanted at the level of the descending respiratory pathways within the C2 spinal cord, can regenerate their axons within the grafts and still transmit normal physiological messages [Decherchi et al., 1996. Exp. Neurol. 137, 1–14]. The present work investigated the extent to which mature central neurons, acutely or chronically axotomized by a spinal lesion, still maintain the potential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures and remained functional. This study is an extension of earlier work employing the more chronic lesions, that investigated whether respiratory neurons chronically axotomized by a spinal cord injury can retain the ability to regenerate their axonal process within a post-traumatic peripheral nerve graft. Here implantation was performed into the supra-lesional ventrolateral part of the ipsilateral C2 spinal cord (at the level of the descending respiratory pathways) previously hemisected at the C3 level. In the present study, these post-traumatic peripheral nerve grafts were performed either acutely (group I, n=15, 2.5 h post-injury: acute conditions) or chronically (group II, n=17, 3 weeks; group III, n=6, 3 months: chronic conditions) after the injury. Electrophysiological recording of teased filaments ( n=2362) within the post-traumatic peripheral nerve grafts revealed the presence of regenerated nerve fibers with spontaneous unitary impulse traffic (graft units, n=954) in all animals. These graft units were respiratory ( n=247) and non-respiratory ( n=707). Respiratory discharges originated from central respiratory neurons which remained functional with preserved afferent connections. Except for the group III, post-traumatic C2 peripheral nerve grafts of the groups I and II contained a significantly higher occurrence rate (13.2±2% and 11.6±1.9%) of respiratory units than C2 spinal peripheral nerve grafts (5.9±1.6%) realized without previous CNS injury. The main conclusion of our study is that for a prolonged period of 3 weeks following a spinal cord injury, central respiratory neurons have the potential to remain functional and to regenerate their axonal process within post-traumatic peripheral nerve grafts inserted rostrally to the spinal damage. This indicates that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of chronically axotomized adult central neurons. This suggests that surgical intervention which is not always possible immediately after a spinal cord injury may be satisfactorily carried out after an appropriate delay.