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Local erythropoietin signaling enhances regeneration in peripheral axons.

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 kappaB (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.

journal_name

Neuroscience

journal_title

Neuroscience

authors

Toth C,Martinez JA,Liu WQ,Diggle J,Guo GF,Ramji N,Mi R,Hoke A,Zochodne DW

doi

10.1016/j.neuroscience.2008.03.052

subject

Has Abstract

pub_date

2008-06-23 00:00:00

pages

767-83

issue

2

eissn

0306-4522

issn

1873-7544

pii

S0306-4522(08)00456-9

journal_volume

154

pub_type

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