Grants Funded

Abstract

Project Summary: Peripheral nerve injuries are common, found in 3% of emergency room patients with limb injury. Despite this relative frequency surgical repair of proximal nerve injuries can result in poor functional outcomes for patients. This is the result of slow nerve regeneration at 1 mm a day coupled with significant distance to overcome. Once the nerve has regenerated to its target 2-3 years later, the muscles are often atrophied and unable to be accept the nerve or be reinnervated. Further, this denervation or a tissue without a nerve has a profound impact on bone demineralization. Bone that is demineralized is weakened placing the limb at risk for fracture after a peripheral nerve injury. Therefore, being able to identify ways to accelerate nerve growth before permanent muscle injury ensues, while promoting bone remineralization and health is crucial. One promising therapy may be exercise training. It has previously been found that exercise can improve the rate of nerve regeneration, preserving muscle, and restoring bone mineralization. As bone is impacted directly by peripheral nerve injury, we believe that bone may have a role in helping nerves regenerate. In order for nerves to regenerate, specific molecules are required to be released to promote regeneration. Bones a target tissue affected by nerve denervation, may be an ideal source of nerve regeneration-enhancing factors. Osteocalcin is a molecule that is released into the bloodstream to promote bone mineralization and muscle hypertrophy. This may represent a molecule that is responsible for bone health and have a role in nerve regeneration. Therefore, we aim to study if bone activation via exercise can promote nerve regeneration. We will aim to determine what the role of osteocalcin plays in the link between bone health and nerve regeneration. We will aim to complete this in animal models that if successful, the discovery of bone-induced nerve regeneration will lay the foundation for new avenues to study nerve regeneration and repair. Success in our clinical findings could have a major impact on postoperative care for all nerve repair surgeries.

Impact Statement: A link between bone health, metabolism, and nerve regeneration has never been previously established. If the proposed study is successful this would represent the first study to show that bone secreted proteins are capable of influencing nerve regeneration. This would open up new pathways to explore to, with the aim of improving peripheral nerve regeneration. Exercise training may be one therapy that can harness this pathway activating bone to promote nerve regeneration and prevent bone demineralization. If successful, this project could will further our understanding of the mechanisms in nerve regeneration and be the foundation of incorporating exercise therapy into clinical practice to improve outcomes for patients with peripheral nerve injury.

Biography
Dr. Matthew Curran is an Assistant Professor in the Division of Plastic Surgery at the University of Alberta. After completion of his undergraduate and medical training at the Memorial University of Newfoundland, he moved to the University of Alberta to complete his plastic surgery training. During this time he completed an MSc in Experimental Surgery under the supervision of Dr. K. Ming Chan focusing on strategies to optimize nerve regeneration. He then went on to complete fellowship training at the Brisbane Hand and Upper Limb Research Institute focusing on surgery of the upper limb including peripheral nerve surgery. His research interests include transitional research aimed at optimizing peripheral nerve regeneration and the outcomes after peripheral nerve surgery. He is supported by an expert team in the field of peripheral nerve regeneration. Dr. Christine Webber is a neuroscientist within the Division of Anatomy at the University of Alberta with 20 years experience working with animal models of peripheral nerve regeneration. Dr. Karyne Rabey is an anthropologist within the Division of Anatomy at the University of Alberta with expertise in gait mechanics, bone health and assessment, . Dr. K. Ming Chan is a clinician scientist within the Division of Physical Medicine with a clinical and research focus on neuromuscular disease, particularly peripheral nerve injury. He has a lengthy track record in translational research to improve peripheral nerve regeneration.