Linked Life Data

15314096

Source:http://linkedlifedata.com/resource/pubmed/id/15314096

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2004-10-18
pubmed:abstractText
AY-9944 (AY) exacerbates chronic recurrent seizures in rats that are analogous to atypical absence epilepsy in humans. The mechanism by which AY affects the slow spike-and-wave discharges associated with these seizures is not known, but is thought to involve inhibition of cholesterol synthesis. We tested the hypothesis that seizures seen with AY are due to significant reduction in brain cholesterol and/or elevated brain 7-dehydrocholesterol by assessing whether three other cholesterol synthesis inhibitors mimic AY seizures in rats. Effects of AY on brain sterols and spike-and-wave discharge duration were compared with those of two other late-stage cholesterol inhibitors [BM 15.766 (BM) and U18666A (UA)] and to an HMG-CoA reductase (early-stage cholesterol) inhibitor, lovastatin. With BM or UA, prolongation of seizure duration and brain sterol changes was similar to that caused by AY. AY effects on both brain sterols and seizure duration were dose-related. Lovastatin, with or without concurrent AY, mimicked AY seizures but reduced brain cholesterol by <10% and did not significantly change brain 7-dehydrocholesterol. Either lovastatin has a different mechanism of action than these late-stage cholesterol inhibitors or the brain sterol changes are not directly responsible for seizures in this model.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-2275
pubmed:author
pubmed:issnType
Print
pubmed:volume
45
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2038-43
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15314096-Animals, pubmed-meshheading:15314096-Body Weight, pubmed-meshheading:15314096-Brain, pubmed-meshheading:15314096-Cholesterol, pubmed-meshheading:15314096-Dehydrocholesterols, pubmed-meshheading:15314096-Dose-Response Relationship, Drug, pubmed-meshheading:15314096-Electrophysiology, pubmed-meshheading:15314096-Enzyme Inhibitors, pubmed-meshheading:15314096-Epilepsy, Absence, pubmed-meshheading:15314096-Hydroxymethylglutaryl-CoA Reductase Inhibitors, pubmed-meshheading:15314096-Lovastatin, pubmed-meshheading:15314096-Models, Biological, pubmed-meshheading:15314096-Rats, pubmed-meshheading:15314096-Rats, Long-Evans, pubmed-meshheading:15314096-Sterols, pubmed-meshheading:15314096-Time Factors, pubmed-meshheading:15314096-trans-1,4-Bis(2-chlorobenzaminomethyl)cyclohexane...
pubmed:year
2004
pubmed:articleTitle
Lovastatin exacerbates atypical absence seizures with only minimal effects on brain sterols.
pubmed:affiliation
Division of Neurology, Brain and Behavior Program, The Hospital for Sick Children, University of Toronto, Toronto, Ontario, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't