Access

You are not currently logged in.

Access your personal account or get JSTOR access through your library or other institution:

login

Log in to your personal account or through your institution.

If You Use a Screen Reader

This content is available through Read Online (Free) program, which relies on page scans. Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.

In vivo Evidence that Erythropoietin Protects Neurons from Ischemic Damage

Masahiro Sakanaka, Tong-Chun Wen, Seiji Matsuda, Seiji Masuda, Emi Morishita, Masaya Nagao and Ryuzo Sasaki
Proceedings of the National Academy of Sciences of the United States of America
Vol. 95, No. 8 (Apr. 14, 1998), pp. 4635-4640
Stable URL: http://www.jstor.org/stable/44949
Page Count: 6
  • Read Online (Free)
  • Subscribe ($19.50)
  • Cite this Item
Since scans are not currently available to screen readers, please contact JSTOR User Support for access. We'll provide a PDF copy for your screen reader.
In vivo Evidence that Erythropoietin Protects Neurons from Ischemic Damage
Preview not available

Abstract

Erythropoietin (EPO) produced by the kidney and the liver (in fetuses) stimulates erythropoiesis. In the central nervous system, neurons express EPO receptor (EPOR) and astrocytes produce EPO. EPO has been shown to protect primary cultured neurons from N-methyl-D-aspartate (NMDA) receptor-mediated glutamate toxicity. Here we report in vivo evidence that EPO protects neurons against ischemia-induced cell death. Infusion of EPO into the lateral ventricles of gerbils prevented ischemia-induced learning disability and rescued hippocampal CA1 neurons from lethal ischemic damage. The neuroprotective action of exogenous EPO was also confirmed by counting synapses in the hippocampal CA1 region. Infusion of soluble EPOR (an extra-cellular domain capable of binding with the ligand) into animals given a mild ischemic treatment that did not produce neuronal damage, caused neuronal degeneration and impaired learning ability, whereas infusion of the heat-denatured soluble EPOR was not detrimental, demonstrating that the endogenous brain EPO is crucial for neuronal survival. The presence of EPO in neuron cultures did not repress a NMDA receptor-mediated increase in intracellular Ca2+, but rescued the neurons from NO-induced death. Taken together EPO may exert its neuroprotective effect by reducing the NO-mediated formation of free radicals or antagonizing their toxicity.

Page Thumbnails

  • Thumbnail: Page 
4635
    4635
  • Thumbnail: Page 
4636
    4636
  • Thumbnail: Page 
4637
    4637
  • Thumbnail: Page 
4638
    4638
  • Thumbnail: Page 
4639
    4639
  • Thumbnail: Page 
4640
    4640