The capacity of central nervous system (CNS) axons to elongate from the spinal cord to the periphery throughout a tubular implant joining the ventral horn of the spinal cord to an avulsed root was investigated in a model of brachial plexus injury. The C5-C7 roots were avulsed by controlled traction and the C6 root was bridged to the spinal cord over a 3 mm gap by the use of a collagen cylinder containing or not containing an autologous nerve segment, or an autologous nerve graft. Nine months later, the functionality and the quality of the axonal regrowth was evaluated by electrophysiology, retrograde labelling of neurons, and histological examination of the gap area. A normal electromyogram of the biceps was observed in all animals where the C6 root was bridged to the spinal cord. The mean average amplitude of the motor evoked potentials was comprised between 17.51 +/- 12.03 microV in animals repaired with a collagen cylinder, and 27.83 +/- 22.62 microV when a nerve segment was introduced in the tube. In nonrepaired animals spontaneous potentials reflecting a muscle denervation were observed at electromyography. Retrograde labelling indicated that a mean number of 58.88 +/- 37.89 spinal cord neurons have reinnervated the biceps in animals repaired with a tube versus 78.38 +/- 62.11 when a nerve segment was introduced in the channel, and 97.25 +/- 56.23 in nerve grafting experiments. Analyses of the repair site showed the presence of numerous myelinated regenerating axons. In conclusion, our results indicate that spinal cord neurons can regenerate through tubular implants over a 3 mm gap, and that this axonal regrowth appeared as effective as in nerve grafting experiments. The combination of an implant and a nerve segment did not significantly increase the regeneration rate.

Object. The authors conducted a study to determine the effects of using a nerve autograft (NAG) to promote and guide axonal regrowth from the rostral spinal cord to the caudal lumbar ventral nerve roots to restore hindlimb motor function in adult marmosets after lower thoracic cord injury. Methods. Nine animals underwent a left-sided hemisection of the spinal cord at T-12 via left-sided T9—L3 hemilaminectomy, with section of all ipsilateral lumbrosacral ventral nerve roots. In the experimental group (five animals), an NAG obtained from the right peroneal nerve was anastomosed with the sectioned and electrophysiologically selected lumbar ventral roots (left L-3 and L-4) controlling the left quadriceps muscle and then implanted into the left ventrolateral T-10 cord. In the control group (four animals), the sectioned/selected lumbar ventral roots were only ligated. After surgery, all marmosets immediately suffered from complete paralysis of their left hindlimb. Five months later, some clinical signs of reinnervation such as tension and resistance began to appear in the paralyzed quadriceps of all experimental animals that received autografts. Nine months postoperatively, three of the five experimental marmosets could maintain their lesioned hindlimb in hip flexion. Muscle action potentials and motor evoked potentials were recorded from the target quadriceps in all experimental marmosets, but these potentials were absent in the control animals. Horseradish peroxidase retrograde labeling from the distal sectioned/reconnected lumbar ventral roots traced 234 ± 178 labeled neurons in the ipsilateral T8–10 ventral horn, mainly close to the NAG tip. Histological analysis showed numerous regenerating axons in this denervated/reconnected nerve root pathway, as well as newly formed motor endplates in the denervated/reinnervated quadriceps. No axonal regeneration was detected in the control animals. Conclusions. These data indicate that the rostral spinal neurons can regrow into the caudal ventral roots through an NAG, thereby innervating the target muscle in adult marmosets after spinal cord injury.

Intraspinally implanting a nerve autograft (NAG) to promote axonal regeneration toward periphery was investigated as a surgical treatment for spinal cord injury in adult rats. Fifteen animals underwent a left hemisection of the spinal cord at T12 level and an intradural section of all ipsilateral lumbar ventral roots. In repaired animals (n = 9), the electrophysiologically selected left L3 and L4 lumbar ventral roots supplying the quadriceps muscle were anastomosed to a NAG. The NAG was taken from the right peroneal nerve and then ventrolaterally implanted into the cord at a level 7 mm rostral to the hemisection. In the control group (n = 6), sectioned lumbar ventral roots were left unrepaired. Nine months later, the animals were assessed with clinical, electrophysiological, and histological examinations. Muscle action potential and motor evoked potential were obtained from the denervated/reinnervated quadriceps in all repaired animals, with a mean amplitude of 918.3+/-328.9 microV and 215.8+/-39.7 microV, respectively. Horseradish peroxidase retrograde labeling from the denervated/repaired lumbar ventral roots, performed in five repaired animals, showed that the mean of labeled neurons, ipsilaterally located in the thoracic ventral horn near the implantation site, was 145.8+/-111.7. Histological analysis showed numerous myelinated axons in the NAG and denervated/repaired lumbar ventral roots of all repaired animals. The study of neuromuscular junctions furthermore confirmed numerous newly formed endplates appearing in the denervated/reinnervated quadriceps. These changes were absent in the control animals. These data indicate that the rostral thoracic spinal motoneurons can innervate the caudal denervated/repaired lumbar ventral roots and the target quadriceps via an implanted NAG, thereby inducing some functional recovery in adult rats after lower thoracic spinal cord injury.

We investigated the spatiotemporal GFAP mRNA expression over a period of 11 days following brain injury in rats caused by impact acceleration, which is known to produce diffuse axonal injury (DAI). We observed widespread GFAP mRNA expression throughout the brain, which was more rapid and intense in the hippocampus. This expression was obvious in most animals 2 days after injury and appeared maximal at day 6. Although it decreased by day 11, the level of expression remained high compared with control levels. We noted slight differences in time of onset and the magnitude of the response between hippocampus and white matter structures or cortical areas. The different mechanisms able to trigger this response are discussed in regard to histopathological changes observed in DAI models.

Intraspinal implantation of a collagen guidance channel (CGC) to promote axon regeneration was investigated in marmosets with brachial plexus injury. After avulsion of the right C5, C6 and C7 spinal roots, a CGC containing (group B) or not (group A) a nerve segment, or a nerve graft (group C), was ventro-laterally implanted into the cord to bridge the ventral horn and the avulsed C6 roots. No spinal cord dysfunction was observed following surgery. Two months later, the postoperative flaccid paralysis of the lesioned arm improved. In five months, a normal electromyogram of the affected biceps muscle was recorded in all repaired animals. Motor evoked potentials were obtained with a mean amplitude of 13.37 +/- 13.66 microV in group A, 13.21 +/- 5.16 microV in group B and 37.14 +/- 35.16 microV in group C. The force of biceps muscle contraction was 27.33 +/- 20.03 g (group A), 24.33 +/- 17.03 g (group B) and 37.38 +/- 21.70 g (group C). Retrograde tracing by horseradish peroxidase showed labelled motoneurons ipsilaterally located in the C5 and C6 ventral horn, nearby the implantation site. The mean labelled neurons was 32.33 +/- 21.13, 219.33 +/- 176.29 and 64.33 +/- 23.54 in group A, B and C respectively. Histological analysis presented numerous myelinated and unmyelinated regenerating axons in the implant of these animals. Statistical analysis did not show significant difference among the three repaired groups. Our results indicate that spinal neurons can regenerate through a CGC to avulsed nerve roots and induce motor recovery in primates.