A novel endogenous erythropoietin mediated pathway prevents axonal degeneration

Sanjay C. Keswani, Ulas Buldanlioglu, Angela Fischer, Nicole Reed, Michelle Polley, Hong Liang, Chunhua Zhou, Christelene Jack, Gerhard J. Leitz, Ahmet Hoke

Research output: Contribution to journalArticle

Abstract

Clinically relevant peripheral neuropathies (such as diabetic and human immunodeficiency virus sensory neuropathies) are characterized by distal axonal degeneration, rather than neuronal death. Here, we describe a novel, endogenous pathway that prevents axonal degeneration. We show that in response to axonal injury, periaxonal Schwann cells release erythropoietin (EPO), which via EPO receptor binding on neurons, prevents axonal degeneration. We demonstrate that the relevant axonal injury signal that stimulates EPO production from surrounding glial cells is nitric oxide. In addition, we show that this endogenous pathway can be therapeutically exploited by administering exogenous EPO. In an animal model of distal axonopathy, systemic EPO administration prevents axonal degeneration, and this is associated with a reduction in limb weakness and neuropathic pain behavior. Our in vivo and in vitro data suggest that EPO prevents axonal degeneration and therefore may be therapeutically useful in a wide variety of human neurological diseases characterized by axonopathy.

Original languageEnglish (US)
Pages (from-to)815-826
Number of pages12
JournalAnnals of Neurology
Volume56
Issue number6
DOIs
StatePublished - Dec 2004

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Erythropoietin
Erythropoietin Receptors
Schwann Cells
Wounds and Injuries
Neuralgia
Peripheral Nervous System Diseases
Neuroglia
Nitric Oxide
Extremities
Animal Models
HIV
Neurons

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Keswani, S. C., Buldanlioglu, U., Fischer, A., Reed, N., Polley, M., Liang, H., ... Hoke, A. (2004). A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. Annals of Neurology, 56(6), 815-826. https://doi.org/10.1002/ana.20285

A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. / Keswani, Sanjay C.; Buldanlioglu, Ulas; Fischer, Angela; Reed, Nicole; Polley, Michelle; Liang, Hong; Zhou, Chunhua; Jack, Christelene; Leitz, Gerhard J.; Hoke, Ahmet.

In: Annals of Neurology, Vol. 56, No. 6, 12.2004, p. 815-826.

Research output: Contribution to journalArticle

Keswani, SC, Buldanlioglu, U, Fischer, A, Reed, N, Polley, M, Liang, H, Zhou, C, Jack, C, Leitz, GJ & Hoke, A 2004, 'A novel endogenous erythropoietin mediated pathway prevents axonal degeneration', Annals of Neurology, vol. 56, no. 6, pp. 815-826. https://doi.org/10.1002/ana.20285
Keswani SC, Buldanlioglu U, Fischer A, Reed N, Polley M, Liang H et al. A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. Annals of Neurology. 2004 Dec;56(6):815-826. https://doi.org/10.1002/ana.20285
Keswani, Sanjay C. ; Buldanlioglu, Ulas ; Fischer, Angela ; Reed, Nicole ; Polley, Michelle ; Liang, Hong ; Zhou, Chunhua ; Jack, Christelene ; Leitz, Gerhard J. ; Hoke, Ahmet. / A novel endogenous erythropoietin mediated pathway prevents axonal degeneration. In: Annals of Neurology. 2004 ; Vol. 56, No. 6. pp. 815-826.
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