The DOI matches its Crossref record; 32 of the 32 references it cites were found in a registry or an index.
Hypoxia-Induced Stroke Tolerance in the Mouse Is Mediated by Erythropoietin
Open accessAbstract
Background and Purpose— Cellular response to hypoxia is mainly controlled by hypoxia-inducible factor 1 (HIF-1). The HIF-1 target gene erythropoietin (EPO) has been described as neuroprotective. Thus, we hypothesize EPO to be an essential mediator of protection in hypoxic preconditioning. Methods— We randomized Sv129 mice into groups for different pretreatments, different hypoxia-ischemia intervals, or different durations of ischemia. For hypoxic preconditioning, the animals were exposed to a hypoxic gas mixture (8% O 2 and 92% N 2 ) for 30, 60, 180, 300, or 360 minutes. At 0, 24, 48, 72, or 144 hours later, we performed middle cerebral artery occlusion and allowed reperfusion after 30, 45, 60, or 120 minutes, or occlusion was left to be permanent. We studied EPO gene expression in brain tissue with a real-time reverse transcriptase-polymerase chain reaction and measured HIF-1 DNA-binding activity with an electrophoretic mobility shift assay. To block endogenously produced EPO, we instilled soluble EPO receptor into the cerebral ventricle. Results— Hypoxic preconditioning for 180 or 300 minutes induced relative tolerance to transient focal cerebral ischemia, as evidenced by a reduction of infarct volumes to 75% or 54% of the control, respectively. Hypoxic pretreatment was effective only when applied 48 or 72 hours before middle cerebral artery occlusion. Sixty minutes after hypoxia, we found a marked activation of HIF-1 DNA-binding activity and a 7-fold induction of EPO transcription. Infusion of soluble EPO receptor significantly reduced the protective effect of hypoxic pretreatment by 40%. Conclusions— Endogenously produced EPO is an essential mediator of ischemic preconditioning.
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Cites
HIF-1: mediator of physiological and pathophysiological responses to hypoxia
Semenza, G. L. (2000) · Journal of Applied Physiology · doi:10.1152/jappl.2000.88.4.1474 · Cited by 1,822
Erythropoietin crosses the blood–brain barrier to protect against experimental brain injury
Brines, M. L., Ghezzi, P., Keenan, S., Agnello, D., de Lanerolle, N. C., Cerami, C., Itri, L. M., & Cerami, A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.19.10526 · Cited by 1,402
‘Ischemic tolerance’ phenomenon found in the brain
Kitagawa, K., Matsumoto, M., Tagaya, M., Hata, R., Ueda, H., Niinobe, M., Handa, N., Fukunaga, R., Kimura, K., Mikoshiba, K., et al. (1990) · Brain Research · doi:10.1016/0006-8993(90)90189-i · Cited by 1,091
Erythropoietin Therapy for Acute Stroke Is Both Safe and Beneficial
Ehrenreich, H., Hasselblatt, M., Dembowski, C., Cepek, L., Lewczuk, P., Stiefel, M., Rustenbeck, H.-H., Breiter, N., Jacob, S., Knerlich, F., et al. (2002) · Molecular Medicine · doi:10.1007/bf03402029 · Cited by 1,028
Erythropoietin prevents neuronal apoptosis after cerebral ischemia and metabolic stress
Sirén, A.-L., Fratelli, M., Brines, M., Goemans, C., Casagrande, S., Lewczuk, P., Keenan, S., Gleiter, C., Pasquali, C., Capobianco, A., et al. (2001) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.051606598 · Cited by 1,019
In vivo evidence that erythropoietin protects neurons from ischemic damage
Sakanaka, M., Wen, T.-C., Matsuda, S., Masuda, S., Morishita, E., Nagao, M., & Sasaki, R. (1998) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.95.8.4635 · Cited by 949
Digicaylioglu, M., & Lipton, S. A. (2001) · Nature · doi:10.1038/35088074 · Cited by 923
A Potential Role for Erythropoietin in Focal Permanent Cerebral Ischemia in Mice
Bernaudin, M., Marti, H. H., Roussel, S., Divoux, D., Nouvelot, A., MacKenzie, E. T., & Petit, E. (1999) · Journal of Cerebral Blood Flow & Metabolism · doi:10.1097/00004647-199906000-00007 · Cited by 715
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Erythropoietin Gene Expression in Human, Monkey and Murine Brain
Marti, H. H., Wenger, R. H., Rivas, L. A., Straumann, U., Oigicaylioglu, M., Henn, V., Yonekawa, Y., Bauer, C., & Gassmann, M. (1996) · European Journal of Neuroscience · doi:10.1111/j.1460-9568.1996.tb01252.x · Cited by 552
Cited by
The Science of Stroke: Mechanisms in Search of Treatments
Moskowitz, M. A., Lo, E. H., & Iadecola, C. (2010) · Neuron · doi:10.1016/j.neuron.2010.07.002 · Cited by 1,930
Cerebral preconditioning and ischaemic tolerance
Gidday, J. M. (2006) · Nature Reviews Neuroscience · doi:10.1038/nrn1927 · Cited by 751
Dirnagl, U., Becker, K., & Meisel, A. (2009) · The Lancet Neurology · doi:10.1016/s1474-4422(09)70054-7 · Cited by 587
Self-citationKell, D. B. (2009) · BMC Medical Genomics · doi:10.1186/1755-8794-2-2 · Cited by 554
Pathophysiology and therapy of experimental stroke
Hossmann, K.-A. (2006) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-006-9008-1 · Cited by 475
Metadata
- Authors
- Prass, K., Scharff, A., Ruscher, K., Löwl, D., Muselmann, C., Victorov, I., Kapinya, K., Dirnagl, U., & Meisel, A.
- Venue
- Stroke
- Published
- 2003-08
- Volume
- 34
- Issue
- 8
- Pages
- 1981-1986
- ISSN
- 0039-2499 (ISSN-L)
- 1524-4628
- OpenAlex
- W2082026532
- Cited by
- 286
- References
- 32
- FWCI
- 10.88
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: Hypoxia-Induced Stroke Tolerance in the Mouse Is Mediated by Erythropoietin. https://app.cochat.ai/papers/10.1161/01.str.0000080381.76409.b2
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- Prass, K., Scharff, A., Ruscher, K., Löwl, D., Muselmann, C., Victorov, I., Kapinya, K., Dirnagl, U., & Meisel, A. (2003). Hypoxia-Induced Stroke Tolerance in the Mouse Is Mediated by Erythropoietin. Stroke. https://doi.org/10.1161/01.str.0000080381.76409.b2
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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