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 accessAbstract
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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Cites
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A Potential Role for Erythropoietin in Focal Permanent Cerebral Ischemia in Mice
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Erythropoietin Gene Expression in Human, Monkey and Murine Brain
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Cited by
Axon degeneration mechanisms: Commonality amid diversity
Coleman, M. (2005) · Nature reviews. Neuroscience · doi:10.1038/nrn1788 · Cited by 819
Cerebral preconditioning and ischaemic tolerance
Gidday, J. M. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1927 · Cited by 751
Kempf, T., Eden, M., Strelau, J., Naguib, M., Willenbockel, C., Tongers, J., Heineke, J., Kotlarz, D., Xu, J., Molkentin, J. D., et al. (2006) · Circulation Research · doi:10.1161/01.res.0000202805.73038.48 · Cited by 651
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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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- 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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