Peripheral nerve injuries represent a major public health problem, seen frequently in patients admitted to level I trauma centers and in as many as 30% of individuals with traumatic brain injuries. A primary goal of intervention in this arena is t hasten recovery so as to restore function as rapidly as possible. Progress towards this goal, however, has been limited. Interestingly, we recently discovered that systemic erythropoietin (EPO) administration speeds functional recovery after experimental crush injury to the sciatic nerve, even when EPO is administered one week after injury. These findings have already led to clinical studies being initiated overseas. Understanding how EPO induces this beneficial effect would enable us to design conditions and dosing strategies that can optimize its therapeutic effects;this is the goal of th3e studies proposed in this application. In the first Specific Aim, we will address the question of whether local delivery of EPO, rather than systemic delivery, will enable us to further enhance recovery and thus set the stage for the development of innovative local delivery methods to enhance/induce repair. The pleiotropic multi-organ effects of EPO, coupled with the surgical and medical focus for local treatment for local traumatic injury argues for a local application of this potent pharmacologic bio-modulator. This, in effect, focuses the effect of EPO directly at the site of injury, eliminating secondary effects and enabling the optimization of treatment in a clinically relevant and targeted manner. In the second Specific Aim, we will test the hypothesis that at least part of the mechanism of EPO action derives from beneficial effects on Schwann cells, the cells that support the function of peripheral nerves by myelinating the axons that run through these nerves. Overall, the identification of target cell(s) of EPO action will better enable us to determine how benefit occurs. In this Specific Aim, we will also begin teasing apart the underlying signaling that supports the impact of EPO, providing a basis for envisioning adjuvant therapies that focus on manipulating the key signaling players in the EPO receptor pathway. The above Specific Aims will represent the research training component of the proposed program to support the transition of Dr. John Elfar MD, a clinician/surgeon who is expanding his academic role to the clinician scientist track. The proposed research training plan is positioned on the backdrop of a robust mentoring and didactic training program that collectively represents a multi- faceted training environment aimed at ensuring successful career transition for Dr. Elfar.

Public Health Relevance

This application lays out a mentoring, research and didactic training program to support the transition of Dr. John Elfar MD, an Orthopaedic Surgeon at the University of Rochester Medical Center, to the clinician scientist track. In addition to specific coursework and mentoring activities, a research program is proposed that aims to test the efficacy of erythropoietin as a novel and innovative therapy for neurorecovery following nerve compression injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08AR060164-02
Application #
8588896
Study Section
Arthritis and Musculoskeletal and Skin Diseases Special Grants Review Committee (AMS)
Program Officer
Panagis, James S
Project Start
2013-01-01
Project End
2017-12-31
Budget Start
2014-01-01
Budget End
2014-12-31
Support Year
2
Fiscal Year
2014
Total Cost
$84,915
Indirect Cost
$6,290
Name
University of Rochester
Department
Orthopedics
Type
Schools of Dentistry
DUNS #
041294109
City
Rochester
State
NY
Country
United States
Zip Code
14627
Lee, D J; Zingman, A; Elfar, J C (2016) The use of interference screw fixation in the modified Brunelli technique for scapholunate dissociation. J Hand Surg Eur Vol 41:110-1
Mahmoud, Mostafa; Hegazy, Mohamed; Khaled, Sherif Ahmed et al. (2016) Radiographic Parameters to Predict Union After Volar Percutaneous Fixation of Herbert Type B1 and B2 Scaphoid Fractures. J Hand Surg Am 41:203-7
Mann, Tobias; Lee, Daniel J; Dahl, Jason et al. (2016) Can Radiocarpal-Spanning Fixation Be Made More Functional by Placing the Wrist in Extension? A Biomechanical Study Under Physiologic Loads. Geriatr Orthop Surg Rehabil 7:23-9
Lander, Sarah T; Coppola, Erin; Tyler, Wakenda et al. (2016) A Peculiar Primary Paraganglioma of the Distal Thumb. J Hand Surg Am 41:e91-4
Maceroli, Michael; Nikkel, Lucas E; Mahmood, Bilal et al. (2016) Total Hip Arthroplasty for Femoral Neck Fractures: Improved Outcomes With Higher Hospital Volumes. J Orthop Trauma 30:597-604
Sundem, Leigh; Chris Tseng, Kuang-Ching; Li, Haiyan et al. (2016) Erythropoietin Enhanced Recovery After Traumatic Nerve Injury: Myelination and Localized Effects. J Hand Surg Am 41:999-1010
Speach, David P; Lee, Daniel J; Reed, Jeffrey D et al. (2016) Is medial elbow pain correlated with cubital tunnel syndrome? An electrodiagnostic study. Muscle Nerve 53:252-4
Geary, Michael B; English, Christopher; Yaseen, Zaneb et al. (2015) Flexor digitorum superficialis repair outside the A2 pulley after zone II laceration: gliding and bowstringing. J Hand Surg Am 40:653-9
Dahl, Jason; Lee, Daniel J; Elfar, John C (2015) Anatomic relationships in distal radius bridge plating: a cadaveric study. Hand (N Y) 10:657-62
Brodell, David W; Jain, Amit; Elfar, John C et al. (2015) National trends in the management of central cord syndrome: an analysis of 16,134 patients. Spine J 15:435-42

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