The use of neurotrophic factors in acellular nerve graft for axonal regeneration after avulsion

Abstract

We have previously shown that intra-neural injection of trophic factors such as glial cell line- derived neurotrophic factor (GDNF), brain derived neurotrophic factors (BDNF) and pleiotrophin (PTN) but not ciliary neurotrophic factor (CNTF) promotes axonal regeneration of avulsed motoneurons into nerve graft in adult rats. To study the action of GDNF, the most potent factor among the rest, we used an acellular nerve graft which was devoid of live cells to prevent interference from the Schwann cells. We injected normal saline or 500ng of GDNF into the frozen-thawed acellular nerve. The nerves were then implanted into the avulsed spinal cord. Axonal regeneration into the acellular nerve was monitored with retrograde labeling at four weeks after operation. Our results showed that motoneurons regenerated into the GDNF -treated nerves but not the saline-treated ones. It also enhanced the survival of motoneurons compared with saline control. When the nerves were examined, Schwann cells were only found in GDNF-treated acellular nerves but not in saline-treated. We speculated that GDNF acts as a chemotactic agent to induce Schwann cell migration and guide the regenerating axons into the nerve graft. Indeed, we found that GDNF induced Schwann cell migration out of the cultured sciatic nerve explants. Time point study showed that Schwann cell migrated into the acellular nerve graft before the entry of regenerating axons. Our study shows the chemotactic role of GDNF on Schwann cells for nerve repair and raises the possibility of using trophic factor-treated acellular nerve as a bridge for spinal cord and distal nerves.