Motoneuron Survival after C7 Nerve Root Avulsion and Replantation in the Adult Rabbit: Effects of Local Ciliary Neurotrophic Factor and Brain-Derived Neurotrophic Factor Application

Abstract

The authors investigated the extent and time course of motoneuron cell death after C7 ventral nerve root avulsion under conditions resembling the trauma mechanism in clinical situations. In addition, they evaluated the effect on motoneuron survival of locally applied ciliary neurotrophic factor and brain-derived neurotrophic factor, with the aim of improving preconditions for successful regeneration of peripheral motor innervation. Forty-four New Zealand White rabbits were operated on using a dorsal approach. The dorsal spinal nerve roots of segment C7 were cut, and the ventral roots were completely pulled out from the spinal cord. In seven experimental groups, ciliary neurotrophic factor, brain-derived neurotrophic factor, or both were applied to the lesion site using different application methods and compared with two control groups. One or 3 weeks after the operation, the animals were euthanized and segments C6 to C8 were studied histologically. In group 9, the avulsed rootlets were replanted into the ventrolateral spinal cord and the effect of replantation on motoneuron survival was assessed at 3 weeks postoperatively. The results indicated that within a period of 7 days, 54.4 +/- 12.1 percent of the motoneurons in segments C6 to C8 died without any therapy. Local application of ciliary neurotrophic factor or brain-derived neurotrophic factor lowered motoneuron loss significantly to 16.9 +/- 14.3 percent and 28.0 +/- 11.4 percent, respectively (p < 0.05). The reduction in motoneuron loss persisted after 3 weeks' survival time (23.1 +/- 4.3 percent in ciliary neurotrophic factor-treated animals, and 22.3 +/- 8.4 percent in brain-derived neurotrophic factor-treated animals, p < 0.05). Survival rates were not significantly higher after treatment with a combination of both factors (motoneuron loss, 33.5 +/- 7.1 percent). The authors conclude that the early application of neurotrophic factors appears to be a promising technique to improve motoneuron survival after nerve root avulsion.