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The DOI matches its Crossref record; 37 of the 37 references it cites were found in a registry or an index.

Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress

Open access
Sirén, Anna-Leena, Fratelli, Maddalena, Brines, Michael, Goemans, Christoph, Casagrande, Simona, Lewczuk, Piotr, Keenan, Sonja, Gleiter, Christoph, Pasquali, Claudio, Capobianco, Annalisa, Mennini, Tiziana, Heumann, Rolf, Cerami, Anthony, Ehrenreich, Hannelore, Ghezzi, Pietro·2001·Proceedings of the National Academy of Sciences

Abstract

Erythropoietin (EPO) promotes neuronal survival after hypoxia and other metabolic insults by largely unknown mechanisms. Apoptosis and necrosis have been proposed as mechanisms of cellular demise, and either could be the target of actions of EPO. This study evaluates whether antiapoptotic mechanisms can account for the neuroprotective actions of EPO. Systemic administration of EPO (5,000 units/kg of body weight, i.p.) after middle-cerebral artery occlusion in rats dramatically reduces the volume of infarction 24 h later, in concert with an almost complete reduction in the number of terminal deoxynucleotidyltransferase-mediated dUTP nick-end labeling of neurons within the ischemic penumbra. In both pure and mixed neuronal cultures, EPO (0.1–10 units/ml) also inhibits apoptosis induced by serum deprivation or kainic acid exposure. Protection requires pretreatment, consistent with the induction of a gene expression program, and is sustained for 3 days without the continued presence of EPO. EPO (0.3 units/ml) also protects hippocampal neurons against hypoxia-induced neuronal death through activation of extracellular signal-regulated kinases and protein kinase Akt-1/protein kinase B. The action of EPO is not limited to directly promoting cell survival, as EPO is trophic but not mitogenic in cultured neuronal cells. These data suggest that inhibition of neuronal apoptosis underlies short latency protective effects of EPO after cerebral ischemia and other brain injuries. The neurotrophic actions suggest there may be longer-latency effects as well. Evaluation of EPO, a compound established as clinically safe, as neuroprotective therapy in acute brain injury is further supported.

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Metadata

Authors
Sirén, A.-L., Fratelli, M., Brines, M., Goemans, C., Casagrande, S., Lewczuk, P., Keenan, S., Gleiter, C., Pasquali, C., Capobianco, A., Mennini, T., Heumann, R., Cerami, A., Ehrenreich, H., & Ghezzi, P.
Venue
Proceedings of the National Academy of Sciences
Published
2001-03-20
Volume
98
Issue
7
Pages
4044-4049
ISSN
  • 0027-8424 (ISSN-L)
  • 1091-6490
OpenAlex
W2162264368
Cited by
1,019
References
37
FWCI
25.29
Type
journal article
Language
en
Open access
green

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CoChat. (2026). Citation check: Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. https://app.cochat.ai/papers/10.1073/pnas.051606598
The paper
Sirén, A.-L., Fratelli, M., Brines, M., Goemans, C., Casagrande, S., Lewczuk, P., Keenan, S., Gleiter, C., Pasquali, C., Capobianco, A., Mennini, T., Heumann, R., Cerami, A., Ehrenreich, H., & Ghezzi, P. (2001). Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.051606598

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