Neuroprotective potential of erythropoietin and darbepoetin alfa in an experimental model of sciatic nerve injury

Laboratory investigation

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  • 1 Neurosurgical Clinic, Department of Clinical Neurosciences, University of Palermo; and
  • | 2 Departments of Anesthesiology,
  • | 3 Clinical and Experimental Medicine and Pharmacology (Section of Pharmacology), and
  • | 4 Internal Medicine, University of Messina, Italy
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Object

The objectives of this study were to examine whether the systemic administration of recombinant human erythropoietin (rHuEPO) and its long-lasting derivative darbepoetin alfa expedited functional recovery in a rat model of sciatic nerve injury, and to compare the effects of these agents in the model.

Methods

Thirty male Sprague–Dawley rats received a crush injury to the left sciatic nerve and subsequently underwent either placebo treatment, daily injections of rHuEPO, or weekly injections of darbepoetin alfa.

Results

Both rHuEPO and darbepoetin alfa were effective in reducing neurological impairment and improving compound muscle action potentials following nerve injury. Darbepoetin alfa, however, shortened the duration of peripheral nerve recovery and facilitated recovery from the neurological and electrophysiological impairment following crush injury significantly better than rHuEPO. Examination of the footprint length factor data revealed that darbepoetin alfa–treated animals recovered preinjury function by postoperative Day 10, 4 days earlier than animals treated with rHuEPO and 11 days earlier than animals treated with placebo.

Conclusions

These results suggest that recovery of neurological function in a model of peripheral nerve injury is more rapid with weekly administration of darbepoetin alfa than with daily rHuEPO treatment. Agents that facilitate nerve regeneration have the potential to limit the extent of motor endplate loss and muscle atrophy. The administration of EPO in its long-lasting recombinant forms affords significant neuroprotection in peripheral nerve injury models and may hold promise for future clinical applications.

Abbreviations used in this paper:

CMAP = compound muscle action potential; EPO = erythropoietin; EPOR = EPO receptor; IL = interleukin; rHuEPO = recombinant human EPO; SSI = static sciatic index; TNF = tumor necrosis factor.

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