|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
8
|
|
pubmed:dateCreated |
2010-8-3
|
|
pubmed:abstractText |
Previous exposure to a nonlethal ischemic insult protects the brain against subsequent harmful ischemia. N-methyl-D-aspartate (NMDA) receptors are a highly studied target of neuroprotection after ischemia. Recently, NMDA receptor subtypes were implicated in neuronal survival and death. We focused on the contribution of NR2A and cyclic-AMP response element (CRE)-binding protein (CREB) signaling to ischemic tolerance using primary cortical neurons. Ischemia in vitro was modeled by oxygen-glucose deprivation (OGD). Ischemic tolerance was induced by applying 45-mins OGD 24 h before 180-mins OGD. Sublethal OGD also induced cross-tolerance against lethal glutamate and hydrogen peroxide. After sublethal OGD, expression of phosphorylated CREB and CRE transcriptional activity were significantly increased. When CRE activity was inhibited by CREB-S133A, a mutant CREB, ischemic tolerance was abolished. Inhibiting NR2A using NVP-AAM077 attenuated preconditioning-induced neuroprotection and correlated with decreased CRE activity levels. Activating NR2A using bicuculline and 4-aminopiridine induced resistance to lethal ischemia accompanied by elevated CRE activity levels, and this effect was abolished by NVP-AAM077. Elevated brain-derived neurotrophic factor (BDNF) transcriptional activities were observed after sublethal OGD and administration of bicuculline and 4-aminopiridine. NR2A-containing NMDA receptors and CREB signaling have important functions in the induction of ischemic tolerance. This may provide potential novel therapeutic strategies to treat ischemic stroke.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-10024352,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-10600750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11425894,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11691980,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11717354,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11893339,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11909726,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11919510,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-11953750,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-12194863,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-12439285,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-12849400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-14568745,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-14743453,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-15234351,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-15356193,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-15369669,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-15580338,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-15647742,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-16641230,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17018022,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17073817,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17088105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17213861,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17234586,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17261713,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17261715,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-17360906,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-18516035,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-18688011,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-18711223,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-19296922,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-19734892,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-1997501,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-2245337,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-7512349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-8461137,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-9016349,
http://linkedlifedata.com/resource/pubmed/commentcorrection/20145658-9581764
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Aug
|
|
pubmed:issn |
1559-7016
|
|
pubmed:author |
|
|
pubmed:issnType |
Electronic
|
|
pubmed:volume |
30
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1441-9
|
|
pubmed:dateRevised |
2011-8-3
|
|
pubmed:meshHeading |
pubmed-meshheading:20145658-Animals,
pubmed-meshheading:20145658-Brain-Derived Neurotrophic Factor,
pubmed-meshheading:20145658-Cells, Cultured,
pubmed-meshheading:20145658-Cyclic AMP Response Element-Binding Protein,
pubmed-meshheading:20145658-Gene Expression Regulation,
pubmed-meshheading:20145658-Ischemia,
pubmed-meshheading:20145658-Ischemic Preconditioning,
pubmed-meshheading:20145658-Mice,
pubmed-meshheading:20145658-Neurons,
pubmed-meshheading:20145658-Phosphorylation,
pubmed-meshheading:20145658-Rats,
pubmed-meshheading:20145658-Rats, Wistar,
pubmed-meshheading:20145658-Receptors, N-Methyl-D-Aspartate
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Activation of NR2A receptors induces ischemic tolerance through CREB signaling.
|
|
pubmed:affiliation |
Department of Neurology, Osaka University Graduate School of Medicine, Osaka, Japan. yterasak@medone.med.osaka-u.ac.jp
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
