Erythropoietin is Neuroprotective During Ongoing Compression and Speeds Recovery Following Surgical Decompression in a Murine Model of Chronic Compression Neuropathy: N/A - Not a clinical study

Abstract

Grant received from: American Foundation for Surgery of the Hand (Hand Surgeon Scientist Award), National Institute of Health grant (# 1 K08 AR060164-01A), Clinical and Translational Science Award (CTSA) grant (# UL1 TR000042), through the University of Rochester School of Medicine & Dentistry, University of Rochester CTSA award (# TL1 TR000096) from the National Center for Advancing Translational Sciences of the National Institutes of Health, University of Rochester Center Goldstein Grant, University of Rochester Laboratory Startup Fund, ART/CTSI Student Research Fellowship Award- salary support for Co-Investigator and medical student, Leigh Sundem There is no financial information to disclose. We previously described erythropoietin’s (EPO) effectiveness in ameliorating the effects of acute peripheral nerve crush. Pilot studies indicate that EPO therapy is an effective neuromodulatory agent for the treatment of chronic nerve compression (CNC) when used as an adjuvant to surgical decompression. This left open the question as to whether pretreatment with EPO during compression would be relevant in reducing the effect of ongoing compression. CNC injury was created in wild-type mice by placing an inert silastic sleeve around the sciatic nerve as in previous work. Decompression surgery was performed at 6 weeks with alternative mice receiving pre-decompressive treatment. Nerve conduction studies were performed weekly before decompression and every 48-hours thereafter until full recovery. Sixty mice were randomized into either a sham-surgery group, saline-treatment control (saline/saline), or 1 of 2 EPO-treatment groups with initiation of EPO at day 0 (EPO/EPO), or week 6 (saline/EPO) in conjunction with surgical decompression. Comparison of NCV was tested with one-way ANOVA followed by Student’s t-test in this dataset, which was normally distributed. During compression, there was a progressive decline in nerve conduction velocity (NCV) as compared to sham-injured animals where NCV remained normal (∼55 m/s) throughout the experiment (Figure 1A). NCV in saline-treated animals progressively decreased from normal (55.153.42 m/s) to a plateau (35.680.72 m/s) over 6 weeks of compression. This expected decline was strikingly attenuated in randomly-selected animals treated with EPO (NCV decreased from 54.091.67 to 45.771.08 m/s, P < 0.01) so that EPO-treated animals fared significantly better than saline-treated counterparts (P < 0.01). Following decompression, all animals recovered to a normal baseline NCV by day 15 (P = 0.74); however, the improvement in NCV observed was markedly accelerated within the first week post-decompression in the EPO-treated groups, and not in saline-treated counterparts (P < 0.01). Animals treated with EPO during both phases fully recovered in half the time as those treated only after decompression (day 5 versus day 9 P < 0.05). •This study supports the possibility of EPO as a neuroprotective agent during CNC injury in rodents and may support adjuvant use during active compression.•Improvement in electrophysiologic parameters is observed with EPO treatment during compression and decompression phases.•EPO may accelerate the natural recovery of decompressed nerves and protect against ongoing injury through the same mechanism, which suggests translational relevance.View Large Image Figure ViewerDownload Hi-res image Download (PPT) This research was supported by a 2013 Hand Surgeon Scientist Award from the American Foundation for Surgery of the Hand.