Modification of the regenerative response of dorsal column axons by olfactory ensheathing cells or peripheral axotomy in adult rat

Abstract

The regeneration of sciatic-dorsal column (DC) axons following DC crush injury and treatment with olfactory ensheathing cells (OECs) and/or sciatic axotomy (“conditioning lesion”) was evaluated. Sciatic-DC axons were examined with a transganglionic tracer, cholera toxin conjugated to horseradish peroxidase, and evaluated at chronic time points, 2–26 weeks post-lesion. With DC injury alone (n = 7), sciatic-DC axons were localized to the caudal border of the lesion terminating in reactive end bulbs with no indication of growth into the lesion. In contrast, treatment with either a heterogeneous population of OECs (equal numbers of p75- and fibronectin-positive OECs) (n = 9) or an enriched population of OECs (75% p75-positive OECs) (n = 6) injected either directly into the lesion or 1-mm rostral and caudal to the injury, stimulated DC axon growth into the lesion. A similar regenerative response was observed with a conditioning lesion either concurrent to (n = 4) or 1 week before (n = 4) the DC injury. In either of the latter two paradigms, some DC axons grew across the injury, but no axons grew into the rostral intact spinal cord. Upon combining OEC treatment with the conditioning lesion (n = 21), the result was additive, increasing DC axon growth beyond the rostral border of the lesion in best cases. Additional factors that may limit DC regeneration were tested including formation of the glial scar (immunoreactivity to glial fibrillary acidic protein in astrocytes and to chondroitin sulfate proteoglycans), which remained similar between treated and untreated groups.