Linked Life Data

18035423

Source:http://linkedlifedata.com/resource/pubmed/id/18035423

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2008-6-27
pubmed:abstractText
Pleiotropic mechanisms beyond their cholesterol lowering effect of 3-hydroxy 3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors or statins such as pravastatin are known. We used a temporary middle cerebral artery occlusion (tMCAO) model in 114 Wistar rats to assess i) whether repeated injections of various doses of pravastatin (0.1, 0.5, 1 and 2 mg/kg) at 30 min, 6 h, 1, 2, 3, and 4 days after stroke onset are neuroprotective, ii) whether attenuation of striatal glutamate and interleukin-6 (IL-6) release is part of the neuroprotective mechanism, and iii) how local cerebral blood flow (CBF) is influenced by pravastatin both in the acute and late stage of ischemia. Animals were sacrificed 5 days after MCAO, infarct size was analyzed with 2,3,5-triphenyltetrazolium chloride (TTC) staining. As compared to saline (139+/-14 mm3, n=11), higher doses of pravastatin beyond 0.1 mg/kg significantly reduced infarct size with the greatest effect obtained with 1 mg/kg (60+/-14 mm3, n=11, P=0.0004). Using cerebral microdialyis in this dose group, we demonstrated that striatal glutamate increase in the ischemic hemisphere was attenuated by pravastatin compared to placebo. Likewise, IL-6 release was diminished at 2 h, but not at 6 h after tMCAO. Improvement of local CBF by pravastatin was observed at day 5, but not at 5 h after tMCAO, thus representing a more long term effect of pravastatin. In conclusion, a relatively high dose of pravastatin administered repetitively after stroke onset improved neurological outcome through various cholesterol-independent mechanisms.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0165-0173
pubmed:author
pubmed:issnType
Print
pubmed:volume
58
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
48-56
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Neuroprotection by pravastatin in acute ischemic stroke in rats.
pubmed:affiliation
Department of Neurology, University of Heidelberg, Germany. christian.berger@urz.uni-heidelberg.de
pubmed:publicationType
Journal Article, Review