Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2004-1-28
pubmed:abstractText
There has been considerable interest in the use of thrombin inhibitors to reduce the occurrence of stroke or to potentiate tissue plasminogen activator-induced reperfusion. However, there is growing evidence that thrombin may also have extravascular effects that influence ischemic brain injury. Male Sprague-Dawley rats were subjected to either 90 minutes of temporary middle cerebral artery (MCA) occlusion or sham operation to examine thrombin and protease activated receptor-1 (PAR-1) expression. In another set of rats, the MCA was occluded for 90 minutes and 10 U of hirudin or the same volume of vehicle was injected into the caudate followed by reperfusion for up to 28 days, to test the effects of local thrombin inhibition on ischemic damage, neurologic outcome and cerebral blood flow (CBF). Thrombin immunoreactivity was increased in the ischemic caudate at 4 and 24 hours, whereas PAR-1 expression was unchanged. Hirudin reduced infarct volume in the caudate at 24 hours (79 +/- 41 vs. 115 +/- 20 mm3, P < 0.05) and resulted in a larger residual tissue volume in the caudate at 28 days (17.6 +/- 3.9 vs. 11.8 +/- 6.3 mm3, P < 0.05). Hirudin treatment also had a beneficial effect on body weight and ameliorated neurologic deficits tested by forelimb placing and forelimb use asymmetry during 28 days survival. These beneficial effects of hirudin were not associated with improved regional CBF during reperfusion. These results suggest that, in addition to their effects on coagulation and circulation, thrombin inhibitors also have direct neuroprotective properties and may be considered in stroke therapy.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0271-678X
pubmed:author
pubmed:issnType
Print
pubmed:volume
24
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
159-66
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2004
pubmed:articleTitle
Intracerebral hirudin injection attenuates ischemic damage and neurologic deficits without altering local cerebral blood flow.
pubmed:affiliation
Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan 48109, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't