TY - JOUR
T1 - Bridging Schwann cell transplants promote axonal regeneration from both the rostral and caudal stumps of transected adult rat spinal cord
AU - Xu, Xiao Ming
AU - Chen, Aqing
AU - Guénard, Véronique
AU - Kleitman, Naomi
AU - Bunge, Mary Bartlett
N1 - Funding Information:
The authors wish to thank Anna Gomez, Margaret Bates, Jean-Pierre Brunschwig, Cesar Vargas, and Andrew Weber for expert technical assistance; Margaret Bates for electron microscope work to obtain the myelinated : unmyelinated axon ratios and to detect axons in Matrigel grafts; Deyanira Santiago for help with animal care; Robert Camarena for photographic assistance; Dr John Klose for help with statistical analysis; Dr Ian Dickerson, Department of Physiology and Biophysics, for the CGRP antibody; Dr Richard Bunge for invaluable discussions; and Charlaine Rowlette for word processing. Dr Stephen Onifer, The Miami Project, advised us on the technique of visualizing tracer-containing axons. This study could not have been done without the gifts of guidance channels from Dr Patrick Aebischer, Univérsité de Lausanne. This work was supported by NIH grants NS28059 and NS09923, and by The Miami Project to Cure Paralysis. Dr Xu was a Daniel Heumann International Scholar.
PY - 1997
Y1 - 1997
N2 - Transplantation of cellular components of the permissive peripheral nerve environment in some types of spinal cord injury holds great promise to support regrowth of axons through the site of injury. In the present study, Schwann cell grafts were positioned between transected stumps of adult rat thoracic spinal cord to test their efficacy to serve as bridges for axonal regeneration. Schwann cells were purified in culture from adult rat sciatic nerve, suspended in Matrigel:DMEM (30:70), and drawn into polymeric guidance channels 8 mm long at a density of 120 x 106 cells ml-1. Adult Fischer rat spinal cords were transected at the T8 cord level and the next caudal segment was removed. Each cut stump was inserted 1 mm into the channel. One month later, a bridge between the severed stumps had been formed, as determined by the gross and histological appearance and the ingrowth of propriospinal axons from both stumps. Propriospinal neurons (mean, 1064 ± 145 SEM) situated as far away as levels C3 and S4 were labelled by retrograde tracing with Fast Blue injected into the bridge. Near the bridge midpoint there was a mean of 1990 ± 594 myelinated axons and eight times as many nonmyelinated, ensheathed axons. Essentially no myelinated or unmyelinated axons were observed in control Matrigel-only grafts. Brainstem neurons were not retrogradely labelled from the graft, consistent with growth of immunoreactive serotonergic and noradrenergic axons only a short distance into the rostral end of the graft, not far enough to reach the tracer placed at the graft midpoint. Anterograde tracing with PHA-L introduced rostral to the graft demonstrated that axons extended the length of the graft but essentially did not leave the graft. This study demonstrates that Schwann cell grafts serve as bridges that support (1) regrowth of both ascending and descending axons across a gap in the adult rat spinal cord and (2) limited regrowth of serotonergic and noradrenergic fibres from the rostral stump. Regrowth of monoaminergic fibres into grafts was not seen in an earlier study of similar grafts placed inside distally capped rather than open-ended channels. Additional intervention will be required to foster growth of the regenerated axons from the graft into the distal cord tissue.
AB - Transplantation of cellular components of the permissive peripheral nerve environment in some types of spinal cord injury holds great promise to support regrowth of axons through the site of injury. In the present study, Schwann cell grafts were positioned between transected stumps of adult rat thoracic spinal cord to test their efficacy to serve as bridges for axonal regeneration. Schwann cells were purified in culture from adult rat sciatic nerve, suspended in Matrigel:DMEM (30:70), and drawn into polymeric guidance channels 8 mm long at a density of 120 x 106 cells ml-1. Adult Fischer rat spinal cords were transected at the T8 cord level and the next caudal segment was removed. Each cut stump was inserted 1 mm into the channel. One month later, a bridge between the severed stumps had been formed, as determined by the gross and histological appearance and the ingrowth of propriospinal axons from both stumps. Propriospinal neurons (mean, 1064 ± 145 SEM) situated as far away as levels C3 and S4 were labelled by retrograde tracing with Fast Blue injected into the bridge. Near the bridge midpoint there was a mean of 1990 ± 594 myelinated axons and eight times as many nonmyelinated, ensheathed axons. Essentially no myelinated or unmyelinated axons were observed in control Matrigel-only grafts. Brainstem neurons were not retrogradely labelled from the graft, consistent with growth of immunoreactive serotonergic and noradrenergic axons only a short distance into the rostral end of the graft, not far enough to reach the tracer placed at the graft midpoint. Anterograde tracing with PHA-L introduced rostral to the graft demonstrated that axons extended the length of the graft but essentially did not leave the graft. This study demonstrates that Schwann cell grafts serve as bridges that support (1) regrowth of both ascending and descending axons across a gap in the adult rat spinal cord and (2) limited regrowth of serotonergic and noradrenergic fibres from the rostral stump. Regrowth of monoaminergic fibres into grafts was not seen in an earlier study of similar grafts placed inside distally capped rather than open-ended channels. Additional intervention will be required to foster growth of the regenerated axons from the graft into the distal cord tissue.
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U2 - 10.1023/A:1018557923309
DO - 10.1023/A:1018557923309
M3 - Article
C2 - 9154524
AN - SCOPUS:0030989043
VL - 26
SP - 1
EP - 16
JO - Journal of Neurocytology
JF - Journal of Neurocytology
SN - 0300-4864
IS - 1
ER -