REGENERATION OF ADULT-RAT SENSORY AXONS INTO INTRASPINAL NERVE GRAFTS- PROMOTING EFFECTS OF CONDITIONING LESION AND GRAFT PREDEGENERATION

The effect of intraspinally implanted predegenerated peripheral nerve grafts and/or conditioning lesions on the regenerative capacity of cen tral ascending sensory axons was investigated in the adult rat. Regene rating sensory fibers were analyzed after their transganglionic labeli ng with cholera toxin B subunit, usually 1 month after implantation. A conditioning lesion (transection of the tibial and peroneal nerve) ca used a fivefold increase in the number of sensory fibers within the fr esh graft when applied on the day of grafting and a sevenfold increase when applied 1 week before. In the latter case, a small portion of th e fibers (10%) had reached the rostral end of the nerve graft. In the absence of a conditioning lesion, the number of fibers regenerating in to a predegenerated nerve graft (collected from the distal part of the peroneal nerve that had been axotomized 1 week earlier) was similar t o that found in a fresh graft. However, predegenerated grafts received three and five times more fibers than a fresh graft when conditioning lesions were applied on or 1 week before the day of grafting. With th e combination of a predegenerated graft and a 1-week conditioning, mos t (> 90%) of the regenerating fibers had reached the rostral graft-hos t border. In animals with a fresh graft, a portion of the axotomized f ibers formed terminal club-like structures. Much fewer fibers displaye d such clubs in animals with a predegenerated graft or a conditioning lesion, suggesting a preventive action of either treatment. A time-cou rse study with the combined treatments showed that regenerating sensor y fibers had already entered the graft after 3 days. Between 1 and 2 w eeks, a maximum number of fibers had reached the rostral end of the ne rve graft. However, after 2 months, the number of fibers was decreased , i.e., the initial advantage of predegeneration had diminished. The c urrent results demonstrate the necessity of a conditioning lesion for successful regeneration of central sensory fibers, possibly resulting from an earlier induction of the neuronal growth response which allows the axon to enter the graft before the formation of a graft-host barr ier. The predegeneration of the nerve graft augments the growth respon se of the axotomized central sensory fibers, probably by providing a m ore supportive terrain and/or enhancement of the neuronal response. Th e presence of a large number of fibers at the rostral graft-host borde r now provides the opportunity to investigate the effects of neurotrop hic factors on the regenerative capacity of the ascending rat sensory fibers into the denervated spinal cord in vivo. (C) 1994 Academic Pres s, Inc.