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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2004-3-9
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pubmed:abstractText |
Pharmacological blockade of NMDA receptor function induces apoptotic neurodegeneration in the developing rat brain. However, the use of NMDA receptor antagonists as anesthetics and sedatives represents a difficult-to-avoid clinical practice in pediatrics. This warrants the search for adjunctive neuroprotective measures that will prevent or ameliorate neurotoxicity of NMDA receptor antagonists. The NMDA receptor antagonist MK801 triggered apoptosis in the neonatal rat forebrain, most notably in cortex and thalamus. MK801 exposure reduced mRNA levels of erythropoietin (EPO) and the EPO receptor, suggesting that loss of endogenous EPO activity may contribute to MK801-induced apoptosis. Coadministration of recombinant EPO (rEPO) conferred 50% neuroprotection, partially restored MK801-induced reduction of brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF) mRNA, and prevented decreased phosphorylation levels of extracellular signal-regulated protein kinase-1/2 (ERK1/2) and Akt. These observations indicate that rEPO partly rescues newborn rats from MK801-mediated brain damage by enhancing neurotrophin-associated signaling pathways.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Akt1 protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Brain-Derived Neurotrophic Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate,
http://linkedlifedata.com/resource/pubmed/chemical/Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/Gdnf protein, rat,
http://linkedlifedata.com/resource/pubmed/chemical/Glial Cell Line-Derived...,
http://linkedlifedata.com/resource/pubmed/chemical/Mitogen-Activated Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Nerve Growth Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-akt,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Messenger,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Erythropoietin,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Fusion Proteins
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pubmed:status |
MEDLINE
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pubmed:month |
Mar
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pubmed:issn |
0969-9961
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
15
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
177-87
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:15006687-Animals,
pubmed-meshheading:15006687-Animals, Newborn,
pubmed-meshheading:15006687-Apoptosis,
pubmed-meshheading:15006687-Brain,
pubmed-meshheading:15006687-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:15006687-Dizocilpine Maleate,
pubmed-meshheading:15006687-Erythropoietin,
pubmed-meshheading:15006687-Excitatory Amino Acid Antagonists,
pubmed-meshheading:15006687-Glial Cell Line-Derived Neurotrophic Factor,
pubmed-meshheading:15006687-Mice,
pubmed-meshheading:15006687-Mice, Transgenic,
pubmed-meshheading:15006687-Mitogen-Activated Protein Kinases,
pubmed-meshheading:15006687-Nerve Degeneration,
pubmed-meshheading:15006687-Nerve Growth Factors,
pubmed-meshheading:15006687-Neuroprotective Agents,
pubmed-meshheading:15006687-Protein-Serine-Threonine Kinases,
pubmed-meshheading:15006687-Proto-Oncogene Proteins,
pubmed-meshheading:15006687-Proto-Oncogene Proteins c-akt,
pubmed-meshheading:15006687-RNA, Messenger,
pubmed-meshheading:15006687-Rats,
pubmed-meshheading:15006687-Rats, Wistar,
pubmed-meshheading:15006687-Receptors, Erythropoietin,
pubmed-meshheading:15006687-Receptors, N-Methyl-D-Aspartate,
pubmed-meshheading:15006687-Recombinant Fusion Proteins,
pubmed-meshheading:15006687-Signal Transduction
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pubmed:year |
2004
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pubmed:articleTitle |
Erythropoietin protects the developing brain against N-methyl-D-aspartate receptor antagonist neurotoxicity.
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pubmed:affiliation |
Department of Neonatology, Charité, Campus Virchow Klinikum, Humboldt University Berlin, Berlin, Germany.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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