Regrowth of acute and chronic injured spinal pathways within supra-lesional post-traumatic nerve grafts

The present work investigates the extent to which mature central neurons ac utely or chronically axotomized by a spinal lesion still maintained the pot ential to regenerate an axon following post-traumatic nerve grafting within supra-lesional spinal structures. In adult rats, a C3 cervical hemisection (injury) was made and an autologous segment of the peroneal nerve was impl anted 2 mm rostrally into the ventrolateral part of the ipsilateral C2 spin al cord. Nerve graft implantations were carried out acutely at the time of injury (group I, acute conditions) or chronically, three weeks post-injury (group II, chronic conditions). Central neurons axotomized by the spinal le sion were labeled by True Blue injected at the lesion site at the time of t rauma. Central neurons regenerating axons within the nerve grafts were labe led with either horseradish peroxidase (only in group I, n = 4) or Nuclear Yellow (group I, n = 3 and group II, n = 6) applied two to four months post -grafting to the distal cut end of the nerve grafts. Neurons with dual stai ning (True Blue/Nuclear Yellow) represented central regenerating neurons wh ich were previously axotomized by the spinal lesion and which had retained the capacity for axonal regeneration for a delayed period after injury. In group I (acute injury conditions), all types of labeled cells were found to be scattered with a clear bimodal distribution within the spinal cord and the brainstem. No labeled cells were found within the motor cortex. There w as no statistically significant difference between horseradish peroxidase a nd all cells containing Nuclear Yellow (Nuclear Yellow and True Blue/Nuclea r Yellow). In group II (chronic injury conditions), Nuclear Yellow- and Tru e Blue/Nuclear Yellow-labeled cells had a similar dual distribution to that of group I, but were found to be significantly less represented (P = 0.019 ). These differences are discussed in terms of capacity for cell survival a nd axonal regrowth after acute and chronic injury. The main conclusion is b ased on the evidence of dual staining of central neurons in both groups, wh ich demonstrates that brainstem and spinal neurons involved in acute and ch ronic axotomy after spinal C3 lesion can survive the trauma and still maint ain the capacity to regenerate lesioned axons within nerve grafts inserted rostrally (C2 spinal cord) to the primary site of injury. Although exhibite d to a lesser extent in chronic than in acute conditions, this capacity was found to occur for as long as three weeks post-injury. These results indicate that supra-lesional post-traumatic nerve grafts may constitute an efficient delayed strategy for inducing axonal regrowth of ch ronically axotomized adult central neurons. We suggest that surgical interv ention; which is not always possible immediately after a spinal cord injury , may be satisfactorily carried out after an appropriate delay. (C) 2000 IB RO. Published by Elsevier Science Ltd. All rights reserved.