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SELECTIVE ENHANCEMENT OF AXONAL INGROWTH IN PROCESSED NERVE ALLOGRAFTS LOADED WITH NEUROTROPHIC FACTORS IN THE RAT SCIATIC NERVE MODEL
Presenter: Presenter: Richard B Boyer, Medical Student
Co-Authors: Sexton KW; Rodriguez-Feo CL; Pollins AC; Cardwell NL; Nanney LB; Shack RB; Thayer WP
Vanderbilt University School of Medicine

Introduction: Peripheral nerve injury is a common source of morbidity in civilian and military trauma. Up to 97% of Sunderland first-degree nerve injuries attain normal functional outcome, however with higher-grade injuries such as complete nerve transection less than 20% have meaningful functional recovery. The most challenging peripheral nerve repairs include injuries with segmental nerve gaps requiring nerve conduits or grafts. The RANGER study has shown processed nerve allografts to perform favorably in nerve gaps between 5 and 50mm. Recent studies from our lab suggest augmentation of processed nerve allografts with neurotrophic factors may accelerate axonal ingrowth. Our hypothesis is that loading allografts with nerve growth factor (NGF) or glial-derived neurotrophic factor (GDNF) will drive selective, motor vs. sensory, axonal ingrowth.

Methods: Sciatic nerves were harvested from 6 Female Sprague Dawley rats and after washing in PBS, were made acellular by three freeze-thaw cycles in liquid nitrogen. The nerves were then incubated in chondroitinase for 16 hours at 37? C. Next, chondroitinase-treated nerves were washed in PBS and incubated for 2 hours in NGF, GDNF, or sterile water. Rats were anesthetized with isoflurane and the left sciatic nerve was exposed. One-centimeter nerve segments were excised and processed allografts were interposed using end-to-end epineurial repair technique. On postoperative day 5 the rats were sacrificed and nerves harvested for immunohistochemical analysis with carbonic anhydrase II (CA2)(sensory axons) and choactase (ChAT)(motor axons).

Results: 4 controls, 4 NGF-loaded and 4 GDNF-loaded allografts were performed. A greater than 3.5-fold increase in mean ChAT-stained axon density was found in the GDNF experimental group (31.92 vs. 6.68 axons/hpf, p=0.04). Insignificant increases in CA2 axon density were found in both NGF and GDNF experimental groups.

Conclusion: Consistent with prior in-vitro studies, GDNF-loaded nerve allografts promote early motor axon regeneration post-axotomy. Additional studies are needed to determine long-term effects of NTF-loaded allografts.


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