METHYLPREDNISOLONE ADMINISTRATION IMPROVES AXONAL REGENERATION INTO SCHWANN-CELL GRAFTS IN TRANSECTED ADULT-RAT THORACIC SPINAL-CORD

Schwann cell (SC) grafts support the regeneration of axons of numerous spinal cord neurons when placed into transected adult rat midthoracic spinal cord. Clinically, methylprednisolone (MP) has been shown to be neuroprotective if administered within 8 h after spinal cord injury. We investigated whether axonal regrowth into SC grafts is enhanced whe n MP is administered at the time of spinal cord transection and SC imp lantation. SCs from adult rat sciatic nerves were purified in culture, suspended in Matrigel, and drawn into semipermeable polymeric channel s. MP (30 mg/kg) or vehicle (control) was administered intravenously a t 5 min, 2 h, and 4 h to adult Fischer rats after transection at T8 an d removal of the next three caudal segments. The rostral cord stump wa s inserted 1 mm into the channel; the distal end of the channel was ca pped. Thirty to forty-five days later, the SC/MP group showed large ti ssue cables in the channels and host cord tissue retained in the rostr al end of the channels. Significantly more myelinated axons (1159 +/- 308) were present at the 5-mm level in SC/MP grafts (n = 6) than in SC /vehicle cables (355 +/- 108, n = 5). More unmyelinated than myelinate d axons (approximately 4:1, n = 3) were resolved in the cables by elec tron microscopy. In the SC/MP group, unlike the SC/vehicle group, sero tonergic and noradrenergic fibers were detected immuno-cytochemically 2.5 and 2.0 mm, respectively, into the graft; astrocytes were also ide ntified at similar distances from the interface. Fast Blue retrograde tracing (SC/MP, n = 4; SC/vehicle, n = 3) showed that more spinal cord neurons (1116 +/- 113 vs 284 +/- 88, respectively) and spinal cord ne urons more distant from the graft (C8 vs C5) responded by extending ax ons into the graft in the presence of MP. Also, very significantly, su praspinal brain stem neurons extended axons into the graft only when M P was administered (mean 46 vs 0, n = 3). These results indicate that MP improves axonal regeneration from both spinal cord and brain stem n eurons into thoracic SC grafts, possibly by reducing secondary host ti ssue loss adjacent to the graft. (C) 1996 Academic Press, Inc.