Erythropoietin enhances the regeneration of traumatized tissue after combined muscle-nerve injury.
BACKGROUND
Erythropoietin (EPO) is a pleiotropic cytokine with neuroprotective, anti-inflammatory, and muscle regenerative properties. The purpose of our study was to analyze the regenerative capacity of systemically applied EPO in a combined muscle-nerve injury model.


METHODS
We performed a crush injury to the left soleus muscle in 84 male Wistar rats. Using an instrumented clamp, the muscle was crushed over its complete length. Simultaneously, the ipsilateral sciatic nerve was sham manipulated or crushed. Upon induction of the trauma, animals received either EPO (E) (single application of 5,000 IU/kg body weight intraperitonial) or vehicle solution (K). After in vivo assessment of mechanical pain according to Frey, thermal hyperalgesia, latency of nerve conduction velocity, and strength of the soleus muscle were analyzed at days 1, 7, and 42 postinjury (n = 7 per group). Cell proliferation and apoptosis were assessed by means of histology and immunohistochemistry.


RESULTS
Combined muscle-nerve injury showed a significant loss of muscle strength, which incompletely recovered within 42 days. Rats treated with EPO showed an increased muscle strength after 7 days and 42 days compared with the control group. Pain behavior was highest in the muscle-nerve injured animals at day 7. EPO decreased the pain and increased nerve conduction velocity. Nerve injury diminished proliferation of muscle cells, whereas simultaneous therapy with EPO resulted in a boost of bromdesoxyuridine-positive cells.


CONCLUSIONS
EPO promoted muscle restoration and enhanced nerve recovery after combined muscle-nerve injury. Thus, EPO might represent an attractive therapeutic option to optimize the posttraumatic course after injury.
Department of Trauma and Reconstructive Surgery, University of Rostock, Rostock, Germany.
Robert
R
Rotter
Christian
C
Kuhn
Ioannis
I
Stratos
Markus
M
Beck
Thomas
T
Mittlmeier
Brigitte
B
Vollmar
D000818:Animals; D003444:Crush Syndrome / Q000188:drug therapy* / Q000473:pathology; D004195:Disease Models, Animal; D004921:Erythropoietin / Q000008:administration & dosage*; D006614:Hindlimb / Q000293:injuries; D007150:Immunohistochemistry; D007274:Injections, Intraperitoneal; D008297:Male; D053580:Muscle Strength / Q000187:drug effects / Q000502:physiology; D018482:Muscle, Skeletal / Q000187:drug effects / Q000293:injuries*; D009416:Nerve Regeneration / Q000502:physiology*; D009431:Neural Conduction / Q000187:drug effects; D059348:Peripheral Nerve Injuries / Q000188:drug therapy* / Q000473:pathology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012038:Regeneration / Q000187:drug effects / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects / Q000473:pathology / Q000502:physiology*; D012680:Sensitivity and Specificity
D004921:Erythropoietin