Reinnervation of the biceps brachii muscle following cotransplantation of fetal spinal cord and autologous peripheral nerve into the injured cervical spinal cord of the adult rat.

ABSTRACT

In order to compensate the loss of motoneurons resulting from severe spinal cord injury and to reestablish peripheral motor connectivity, solid pieces of fetal spinal cord, taken from embryonic day 14 rat embryos, were transplanted into unilateral aspiration lesions of the cervical spinal cord of adult rats. Concomitantly, one end of a 3.5-cm autologous peripheral nerve graft was put in close contact with the embryonic graft; the other end was sutured to the distal stump of the musculocutaneous nerve which innervate the biceps brachii muscle. The animals were examined 3 and 6 months after surgery. Following intramuscular injection of horseradish peroxidase, retrograde axonal labeling studies indicated that both transplanted and host spinal neurons were able to extend axons all the way through the peripheral nerve graft and nerve stump, up to the reconnected muscles. The labeled cells in the transplant were generally observed close to the intraspinal tip of the peripheral nerve graft. Retrograde axonal tracing, as well as electrophysiological and histological data, demonstrated the sensory and motor reinnervation of the reconnected muscles. This muscular reinnervation was able to reverse the atrophic changes observed in the denervated muscle. In control experiments, the extraspinal end of the peripheral nerve graft was ligatured in order to compare the differentiation of the transplanted neurons and the survival of their growing axons with or without their muscular targets. Six months after both types of surgery, large-size grafted neurons, identified as motoneurons by immunocytochemistry for peripherine and calcitonin gene-related peptide, were only observed in fetal spinal cord transplants which were connected to denervated muscles, thus demonstrating the trophic influence of the muscle target on the survival and differentiation of the transplanted neurons and on the maintenance of the axons they had grown into the peripheral nerve graft.