Michael B Geary1, Haiyan Li1, Alissa Zingman2, John Ketz2, Michael Zuscik1, Karen L De Mesy Bentley1,3, Mark Noble4, John C Elfar1,2. 1. Center for Musculoskeletal Research, University of Rochester Medical Center, 601 Elmwood Avenue, Box 665, Rochester, New York, 14642, USA. 2. Department of Orthopaedics and Rehabilitation, University of Rochester Medical Center, Rochester, New York, USA. 3. Department of Pathology and Laboratory Medicine, University of Rochester Medical Center, Rochester, New York, USA. 4. Department of Biomedical Genetics, Stem Cell Regenerative Medicine Institute, University of Rochester Medical Center, Rochester, New York, USA.
Abstract
INTRODUCTION: Erythropoietin (EPO) has been identified as a neuroregenerative agent. We hypothesize that it may accelerate recovery after crush injury and may vary with crush severity. METHODS: Mice were randomized to mild, moderate, or severe crush of the sciatic nerve and were treated with EPO or vehicle control after injury. The sciatic function index (SFI) was monitored over the first week. Microstructural changes were analyzed by immunofluorescence for neurofilament (NF) and myelin (P0 ), and electron microscopy was used to assess ultrastructural changes. RESULTS: In moderate crush injuries, EPO significantly improved SFI at 7 days post-injury, an effect not observed with other severity levels. Increases in the ratio of P0 to NF were observed after EPO treatment in moderate crush injuries. Electron microscopy demonstrated endothelial cell hypertrophy in the EPO group. CONCLUSIONS: EPO accelerates recovery in moderately crushed nerves, which may be through effects on myelination and vascularization. Injury severity may influence the efficacy of EPO. Muscle Nerve 56: 143-151, 2017.
INTRODUCTION:Erythropoietin (EPO) has been identified as a neuroregenerative agent. We hypothesize that it may accelerate recovery after crush injury and may vary with crush severity. METHODS:Mice were randomized to mild, moderate, or severe crush of the sciatic nerve and were treated with EPO or vehicle control after injury. The sciatic function index (SFI) was monitored over the first week. Microstructural changes were analyzed by immunofluorescence for neurofilament (NF) and myelin (P0 ), and electron microscopy was used to assess ultrastructural changes. RESULTS: In moderate crush injuries, EPO significantly improved SFI at 7 days post-injury, an effect not observed with other severity levels. Increases in the ratio of P0 to NF were observed after EPO treatment in moderate crush injuries. Electron microscopy demonstrated endothelial cell hypertrophy in the EPO group. CONCLUSIONS:EPO accelerates recovery in moderately crushed nerves, which may be through effects on myelination and vascularization. Injury severity may influence the efficacy of EPO. Muscle Nerve 56: 143-151, 2017.
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