Linked Life Data

17316578

Source:http://linkedlifedata.com/resource/pubmed/id/17316578

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2007-3-26
pubmed:abstractText
FK-506 confers a neuroprotective effect and is thought to extend the time window for thrombolytic treatment of cerebral ischemia. These effects have not been assessed in an embolic stroke model. In addition, clinical studies have raised concern that FK-506 may increase the risk of hemorrhagic transformation by damaging vascular endothelial cells. We investigated whether combined administration of recombinant tissue plasminogen activator (rt-PA) and FK-506 would extend the therapeutic time window without increasing the hemorrhagic transformation in a rat embolic stroke model. Male Sprague-Dawley rats (n=66) were subjected to embolic infarction and assigned into eight groups. Six of the groups were treated with or without FK-506 (0.3 mg/kg) administration at 60 min after embolization, together with and all six groups received systemic rt-PA administration (10 mg/kg) at 60, 90, or 120 min. Two permanent ischemia groups were administered saline either with or without FK-506. Infarct and hemorrhagic volume were assessed at 24 h after embolization. Diffusion-weighted and perfusion-weighted magnetic resonance imaging (MRI) were performed in the groups administered rt-PA at 90 min and a vehicle control group to assess whether FK-506 influenced the effectiveness of MRI in revealing ischemic lesion. FK-506 extended the therapeutic time window for systemic thrombolysis compared to rt-PA alone without increasing the risk for hemorrhage. Combined therapy with FK-506 salvaged some of the MRI, revealing ischemic lesions destined to infarction in the animals treated by rt-PA alone. Single low dose of FK-506 alone did not ameliorate the embolic infarction, but it did prove effective in extending the therapeutic time windows for thrombolysis without increasing the risk of hemorrhagic transformation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
27
pubmed:volume
1143
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
221-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
FK-506 extended the therapeutic time window for thrombolysis without increasing the risk of hemorrhagic transformation in an embolic rat stroke model.
pubmed:affiliation
Division of Neurology, Nephrology and Rheumatology, Department of Internal Medicine, Nippon Medical School, 1-1-5 Sendagi, Bunkyo-ku, Tokyo 113-8603, Japan.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't