Regeneration of Adult Rat Corticospinal Axons Induced by Transplanted Olfactory Ensheathing Cells

Abstract

Precisely localized focal stereotaxic electrolytic lesions were made in the corticospinal tract at the level of the first to second cervical segments in the adult rat. This consistently destroyed all central nervous tissue elements (axons, astrocytes, oligodendrocytes, microglia, and microvessels) in a highly circumscribed area. In a group of these rats immediately after lesioning, a suspension of cultured adult olfactory ensheathing cells was transplanted into the lesion site. Within the first week after transplantation, the cut corticospinal axons (identified by anterograde transport of biotin dextran) extended caudally along the axis of the corticospinal tract as single, fine, minimally branched sprouts that ended in a simple tip, often preceded by a small varicosity. By 3 weeks, the regenerating axons, ensheathed by P0-positive peripheral myelin had accumulated into parallel bundles, which now extended across the full length of the lesioned area and reentered the caudal part of the host corticospinal tract. The transplants contained two main types of cells: (1) p75-expressing S cells, which later formed typical peripheral one-to-one myelin sheaths around individual ensheathed axons, and (2) fibronectin-expressing A cells, which aggregated into tubular sheaths enclosing bundles of myelinated axons. The point of reentry of the axons into the central nervous territory of the caudal host corticospinal tract was marked by the resumption of oligodendrocytic myelination. Thus the effect of the transplant was to form a "patch" of peripheral-type tissue across which the cut central axons regenerated and then continued to grow along their original central pathway.