The effects of Dexamethasone and Erythropoietin on sciatic nerve crush injury in mice

Abstract

Objectives: Peripheral neuropathies are one of the major causes of motor and sensory disability, which have a devastating impact on a patient's quality of life and social and personal cost. Despite decades of research, functional recovery is often unsatisfactory after nerve repair. The multitude of these injuries and associated comorbidities provide a strong impetus to develop agents and methods to accelerate axonal regeneration. Systemic drug delivery is a promising strategy in this regard. This study aimed to evaluate dexamethasone and erythropoietin's effects on nerve regeneration.

Experimental design: Twenty-three mice were randomly assigned to dexamethasone, erythropoietin, dexamethasone\erythropoietin, control, and sham groups. Left sciatic nerve crush injury was created using hemostatic forceps for 10 seconds. Medications were administered once daily for 28 days. Sham operation animals received neither crush injury nor medication. Histopathologic and walking track analyses were performed.

Results: The acquisition of complete return to near normal function with earlier onset of functional recovery in the dexamethasone group, was seen after 28 days regardless of medication used. Histopathologically, the average axonal number was recovered up to 75% normal nerve in erythropoietin and dexamethasone/erythropoietin groups which were statistically significant compared to the control group. Immunoreactivity to s100 protein was observed in regenerated nerves in all groups, furthermore marked immunoreactivity to GFAP was present in the dexamethasone group.

Conclusion: Present data provide new insights into the neurotrophic effects of dexamethasone, erythropoietin, and the combination of these two on sciatic crush injury and support the clinical application of these agents, but no statistically significant synergistic effect of drugs was observed.