Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-3-30
pubmed:abstractText
Thiazolidinediones (TZDs) are synthetic agonists of the ligand-activated transcription factor peroxisome proliferator-activated receptor-gamma (PPARgamma). TZDs are known to curtail inflammation associated with peripheral organ ischemia. As inflammation precipitates the neuronal death after stroke, we tested the efficacy of TZDs in preventing brain damage following transient middle cerebral artery occlusion (MCAO) in adult rodents. As hypertension and diabetes complicate the stroke outcome, we also evaluated the efficacy of TZDs in hypertensive rats and type-2 diabetic mice subjected to transient MCAO. Pre-treatment as well as post-treatment with TZDs rosiglitazone and pioglitazone significantly decreased the infarct volume and neurological deficits in normotensive, normoglycemic, hypertensive and hyperglycemic rodents. Rosiglitazone neuroprotection was not enhanced by retinoic acid x receptor agonist 9-cis-retinoic acid, but was prevented by PPARgamma antagonist GW9662. Rosiglitazone significantly decreased the post-ischemic intercellular adhesion molecule-1 expression and extravasation of macrophages and neutrophils into brain. Rosiglitazone treatment curtailed the post-ischemic expression of the pro-inflammatory genes interleukin-1beta, interleukin-6, macrophage inflammatory protein-1alpha, monocyte chemoattractant protein-1, cyclooxygenase-2, inducible nitric oxide synthase, early growth response-1, CCAAT/enhancer binding protein-beta and nuclear factor-kappa B, and increased the expression of the anti-oxidant enzymes catalase and copper/zinc-superoxide dismutase. Rosiglitazone also increased the expression of the anti-inflammatory gene suppressor of cytokine signaling-3 and prevented the phosphorylation of the transcription factor signal transducer and activator of transcription-3 after focal ischemia. Thus, PPARgamma activation with TZDs might be a potent therapeutic option for preventing inflammation and neuronal damage after stroke with promise in diabetic and hypertensive subjects.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2-chloro-5-nitrobenzanilide, http://linkedlifedata.com/resource/pubmed/chemical/Anilides, http://linkedlifedata.com/resource/pubmed/chemical/Cytokines, http://linkedlifedata.com/resource/pubmed/chemical/Intercellular Adhesion Molecule-1, http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents, http://linkedlifedata.com/resource/pubmed/chemical/PPAR gamma, http://linkedlifedata.com/resource/pubmed/chemical/Socs3 protein, rat, http://linkedlifedata.com/resource/pubmed/chemical/Superoxide Dismutase, http://linkedlifedata.com/resource/pubmed/chemical/Suppressor of Cytokine Signaling..., http://linkedlifedata.com/resource/pubmed/chemical/Thiazolidinediones, http://linkedlifedata.com/resource/pubmed/chemical/pioglitazone, http://linkedlifedata.com/resource/pubmed/chemical/rosiglitazone, http://linkedlifedata.com/resource/pubmed/chemical/superoxide dismutase 1
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
101
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
41-56
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed-meshheading:17394460-Anilides, pubmed-meshheading:17394460-Animals, pubmed-meshheading:17394460-Cerebral Infarction, pubmed-meshheading:17394460-Chemotaxis, Leukocyte, pubmed-meshheading:17394460-Cytokines, pubmed-meshheading:17394460-Diabetes Mellitus, Type 2, pubmed-meshheading:17394460-Disease Models, Animal, pubmed-meshheading:17394460-Encephalitis, pubmed-meshheading:17394460-Hypertension, pubmed-meshheading:17394460-Intercellular Adhesion Molecule-1, pubmed-meshheading:17394460-Ischemic Attack, Transient, pubmed-meshheading:17394460-Mice, pubmed-meshheading:17394460-Mice, Inbred C57BL, pubmed-meshheading:17394460-Mice, Mutant Strains, pubmed-meshheading:17394460-Neuroprotective Agents, pubmed-meshheading:17394460-PPAR gamma, pubmed-meshheading:17394460-Rats, pubmed-meshheading:17394460-Rats, Inbred SHR, pubmed-meshheading:17394460-Rats, Sprague-Dawley, pubmed-meshheading:17394460-Superoxide Dismutase, pubmed-meshheading:17394460-Suppressor of Cytokine Signaling Proteins, pubmed-meshheading:17394460-Thiazolidinediones
pubmed:year
2007
pubmed:articleTitle
Peroxisome proliferator-activated receptor-gamma agonists induce neuroprotection following transient focal ischemia in normotensive, normoglycemic as well as hypertensive and type-2 diabetic rodents.
pubmed:affiliation
Department of Neurological Surgery, University of Wisconsin, Madison, Wisconsin 53792, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural