The Journal of Bone and Joint Surgery (American). 2008;90:1644-1653.
doi:10.2106/JBJS.G.00557
© 2008 The Journal of Bone and Joint Surgery, Inc.
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Erythropoietin Accelerates Functional Recovery After Peripheral Nerve Injury

John C. Elfar, MD1, Justin A. Jacobson, MD1, J. Edward Puzas, PhD1, Randy N. Rosier, MD, PhD1 and Michael J. Zuscik, PhD1

1 Department of Orthopaedics and Rehabilitation, University of Rochester, 601 Elmwood Avenue, Rochester, NY 14620. E-mail address for J.A. Jacobson: Justin_Jacobson{at}urmc.rochester.edu

Investigation performed at the Department of Orthopaedics and Rehabilitation and the Center for Musculoskeletal Research, University of Rochester, Rochester, New York

Disclosure: The authors did not receive any outside funding or grants in support of their research for or preparation of this work. Neither they nor a member of their immediate families received payments or other benefits or a commitment or agreement to provide such benefits from a commercial entity. No commercial entity paid or directed, or agreed to pay or direct, any benefits to any research fund, foundation, division, center, clinical practice, or other charitable or nonprofit organization with which the authors, or a member of their immediate families, are affiliated or associated.

Background: Erythropoietin is a naturally occurring hormone with multiple effects on a number of different cell types. Recent data have suggested neuroprotective and perhaps even neurotrophic roles for erythropoietin. We hypothesized that these functional effects could be demonstrable in standard models of peripheral nerve injury.

Methods: Experiments were undertaken to evaluate the effect of erythropoietin on the previously reported standard course of healing of sciatic injuries in mice. The injury groups included mice that were subjected to (1) sham surgery, (2) a calibrated sciatic crush injury, (3) transection of the sciatic nerve followed by epineural repair, or (4) a transection followed by burial of the proximal stump in the adjacent muscle tissue (neurectomy). Either erythropoietin or saline solution was administered to the mice in each of these experimental groups twenty-four hours preinjury, immediately after surgical creation of the injury, twenty-four hours postinjury, or one week postinjury. All mice were evaluated on the basis of the published model for recovery of sciatic nerve motor function by measuring footprint parameters at specific times after the injury. Immunohistochemistry was also performed to assess the erythropoietin-receptor expression profile at the site of injury.

Results: In general, the mice treated with erythropoietin recovered sciatic nerve motor function significantly faster than did the untreated controls. This conclusion was based on a sciatic function index that was 60% better in the erythropoietin-treated mice at seven days postinjury (p < 0.05). Although the group that had been given the erythropoietin immediately postinjury showed the best enhancement of recovery, the timing of the administration of the drug was not critical. Histological analysis demonstrated enhanced erythropoietin-receptor positivity in the nerves that recovered fastest, suggesting that accelerated healing correlates with expression of the receptor in nerve tissue.

Conclusions: Erythropoietin treatment of an acute sciatic nerve crush injury leads to an effect consistent with functional neuroprotection. This protective effect may have clinical relevance, especially since it was detectable even when erythropoietin had been administered up to one week after injury.

Clinical Relevance: Erythropoietin may represent a safe therapeutic agent to enhance nerve recovery in humans either after or before "nerve-at-risk" procedures as well as a useful adjunct to treatment of peripheral nerve crush injuries.


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