Implantation of neurotrophic factor-treated sensory nerve graft enhances survival and axonal regeneration of motoneurons after spinal root avulsion.

Abstract

We previously showed that motor nerves are superior to sensory nerves in promoting axon regeneration after spinal root avulsion. It is, however, impractical to use motor nerves as grafts. One potential approach to enhancing axonal regeneration using sensory nerves is to deliver trophic factors to the graft. Here, we examined the regulation of receptors for brain-derived neurotrophic factor, glial cell line-derived neurotrophic factor, ciliary neurotrophic factor, and pleiotrophin after root avulsion in adult rats. We then tested their survival-promoting and neuroregenerative effects on spinal motoneurons. The results showed that receptors for brain-derived neurotrophic factor and glial cell line-derived neurotrophic factor were upregulated and that these trophic factors promoted survival and axonal regeneration of motoneurons when they were injected into the sensory nerve graft before implantation. In contrast, receptors for ciliary neurotrophic factor and pleiotrophin were downregulated after avulsion. Ciliary neurotrophic factor did not promote survival and axonal regeneration, whereas pleiotrophin promoted axonal regeneration but not survival of injured spinal motoneurons. Our results suggest that infusion of trophic factors into sensory nerve grafts promote motoneuron survival and axonal regeneration. The technique is technically easy and is, therefore, potentially clinically applicable.