BRIDGING SCHWANN-CELL TRANSPLANTS PROMOTE AXONAL REGENERATION FROM BOTH THE ROSTRAL AND CAUDAL STUMPS OF TRANSECTED ADULT-RAT SPINAL-CORD

Transplantation of cellular components of the permissive peripheral ne rve environment in some types of spinal cord injury holds great promis e to support regrowth of axons through the site of injury. In the pres ent study, Schwann cell grafts were positioned between transected stum ps of adult rat thoracic spinal cord to test their efficacy to serve a s bridges for axonal regeneration. Schwann cells were purified in cult ure from adult rat sciatic nerve, suspended in Matrigel:DMEM (30:70), and drawn into polymeric guidance channels 8 mm long at a density of 1 20 x 10(6) cells ml(-1). Adult Fischer rat spinal cords were transecte d at the T8 cord level and the next caudal segment was removed. Each c ut stump was inserted 1 mm into the channel. One month later, a bridge between the severed stumps had been formed, as determined by the gros s and histological appearance and the ingrowth of propriospinal axons from both stumps. Propriospinal neurons (mean, 1064 +/- 145 SEM) situa ted as far away as levels C3 and S4 were labelled by retrograde tracin g with Fast Blue injected into the bridge. Near the bridge midpoint th ere was a mean of 1990 +/- 594 myelinated axons and eight times as man y nonmyelinated, ensheathed axons. Essentially no myelinated or unmyel inated 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 re ach 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 sup port (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 monoamine rgic fibres into grafts was not seen in an earlier study of similar gr afts placed inside distally capped rather than open-ended channels. Ad ditional intervention will be required to foster growth of the regener ated axons from the graft into the distal cord tissue.