Central nervous system axonal regeneration into sciatic nerve grafts: physiological properties of the grafts and histologic findings in the neuraxis.

Autologous nerve grafts were implanted extraspinally between the medulla and the ipsilateral cervical spinal cord in adult rats. Four to eight months after implantation, electrical stimulation of the grafts evoked EMG activity in a variety of head and neck muscles in 8/10 rats. In 5/10 rats, electrical stimulation of the graft during inspiration potentiated or inhibited EMG activity in each of the diaphragms. After the recordings were completed, the grafts were cut and their ends soaked in horseradish peroxidase (HRP). The average count of HRP-labeled neurons, both in the spinal cord and brain stem, was 969 (252 to 1961). Most labeled neurons were located within +/- 2 mm of the implant sites, with labeling seen in neurons as far as 9 mm away. In the brain stem, 20 different nuclei were labeled. Among them were the reticular formation, raphe complex, cranial nerve nuclei, the subceruleus, ventrolateral pontine tegmentum regions, and contralateral red nucleus. These results in adult rats showed that (i) CNS axons elongating within peripheral nerve grafts were able to conduct action potentials and maintain functional synapses on CNS neurons; (ii) newly growing neurons were situated in close proximity to the nerve graft; and (iii) many different kinds of central neurons, including monoaminergic and descending spinal tract neurons, can elongate their axons into peripheral nerve grafts.