Introduction: Peripheral nerve grafts (PNGs) in the spinal cord support axon regeneration and functional recovery. We are testing a combination of PNGs and a sustained release of neurotrophin-3 (NT-3), that has been shown to induce axonal sprouting, promote axonal growth, and enhance neuroprotection. The sustained release of NT-3 will be from biomineral coated suture.Funding by a grant from the Bryon Riesch Paralysis Foundation.
Methods: NT-3 was bound to Biomineral coated 7-0 vicryl sutures. To test the release profile, the sutures were incubated in simulated body fluid at 37°C for 20 days. Every two days the amount of NT-3 in the release medium was quantified using an ELISA kit.
To test the biomineral coated sutures in vivo, five groups of Lewis rats received complete spinal cord injuries (SCI) at the T10 level: 1) controls; 2) PNGs; 3) PNGs plus biomineral coated sutures; 4) PNGs plus NT-3 injection; and 5) PNGs plus biomineral coated sutures releasing NT-3. Behavioral testing was done before grafting and every week following for eight weeks. To analyze axon regeneration axon tracers were injected into the motor cortex, brainstem (Biotinylated Dextran Amine: BDA) and sciatic nerves (Cholera Toxin B: CTB).
Results: In vitro there was a burst release of NT-3 followed by a sustained linear release for at least 20 days. Groups 2, 3 & 5 all had significantly higher (P<0.05) BBB scores than the controls 8 weeks after grafting. There was no significant difference in function between groups 2, 3, 4 and 5. Both BDA and CTB were observed in the grafts.
Conclusions: The treated groups did better than the control group as far as the BBB scores. Sustained NT-3 release did not provide significant additional benefit to simple PNGs. Future studies will involve testing NT-3 in other species (Sprague-Dawley rats), and in combination with other therapies like Chondroitinase ABC.
Patient Care: Better understanding and treatment of spinal cord injury. If we prove that NT3 improves outcomes after SCI, whether alone or in combination therapy, this would potentially be a clinical therapeutic option for SCI.
Learning Objectives: 1. Peripheral nerve grafts support axonal growth after SCI.
2. NT3 use is safe in rats.
3. Combination therapy is probably key in treating SCI.