Local erythropoietin signaling enhances regeneration in peripheral axons

C. Toth, J. A. Martinez, W. Q. Liu, J. Diggle, G. F. Guo, N. Ramji, R. Mi, A. Hoke, D. W. Zochodne

Research output: Contribution to journalArticle

Abstract

Erythropoietin (EPO) and its receptor (EPO-R), mediate neuroprotection from axonopathy and apoptosis in the peripheral nervous system (PNS). We examined the impact and potential mechanisms of local EPO signaling on regenerating PNS axons in vivo and in vitro. As a consequence of injury, peripheral nerve axons and DRG neurons have a marked increase in the expression of EPO and EPO-R. Local delivery of EPO via conduit over 2 weeks to rat sciatic nerve following crush injury increased the density and maturity of regenerating myelinated axons growing distally from the crush site. In addition, EPO also rescued retrograde degeneration and atrophy of axons. EPO substantially increased the density and intensity of calcitonin gene-related peptide (CGRP) expression within outgrowing axons. Behavioral improvements in sensorimotor function also occurred in rats exposed to near nerve EPO delivery. EPO delivery led to decreased nuclear factor κB (NFkB) activation but increased phosphorylation of Akt and STAT3 within nerve and dorsal root ganglia neurons indicating rescue from an injury phenotype. Spinal cord explant studies also demonstrated a similar dose-dependent effect of EPO upon motor axonal outgrowth. Local EPO signaling enhances regenerating peripheral nervous system axons in addition to its known neuroprotection. Exogenous EPO may have a therapeutic role in a large number of peripheral nerve diseases through its impact on regeneration.

Original languageEnglish (US)
Pages (from-to)767-783
Number of pages17
JournalNeuroscience
Volume154
Issue number2
DOIs
StatePublished - Jun 23 2008

Keywords

  • erythropoietin
  • erythropoietin receptor
  • nerve injury
  • nerve regeneration

ASJC Scopus subject areas

  • Neuroscience(all)

Fingerprint Dive into the research topics of 'Local erythropoietin signaling enhances regeneration in peripheral axons'. Together they form a unique fingerprint.

  • Cite this

    Toth, C., Martinez, J. A., Liu, W. Q., Diggle, J., Guo, G. F., Ramji, N., Mi, R., Hoke, A., & Zochodne, D. W. (2008). Local erythropoietin signaling enhances regeneration in peripheral axons. Neuroscience, 154(2), 767-783. https://doi.org/10.1016/j.neuroscience.2008.03.052