Linked Life Data

17123488

Source:http://linkedlifedata.com/resource/pubmed/id/17123488

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2007-1-12
pubmed:abstractText
The neuroprotective potential and therapeutic time window for fasudil, a Rho-kinase inhibitor (RKI), were evaluated for delayed neuronal death in gerbils. A preliminary screening was done on fasudil, ozagrel, and edaravone using a single administration in a delayed neuronal death study. Intraperitoneal (i.p.) administration of edaravone, a free radical scavenger (3, 10 mg/kg) immediately after re-circulation did not reduce neuronal degeneration. We previously reported that ozagrel, a thromboxane A(2) synthetase inhibitor (30 mg/kg) also did not reduce neuronal degeneration, while fasudil (3, 30 mg/kg) significantly protected against the ischemia-induced neuronal loss. To clarify the therapeutic time window of fasudil, which showed a positive effect in a preliminary screening, animals received their first i.p. administration of fasudil (10 mg/kg) 24 or 48 h after ischemia. Administration of fasudil twice daily was continued until day 6. Fasudil significantly protected against the ischemia-induced delayed neuronal death when the treatment was started 24 h after ischemia. In gerbils, hydroxyfasudil, an active metabolite of fasudil, was found following an i.p. administration of fasudil (10 mg/kg), and the value of the area under the plasma level curve of hydroxyfasudil was 7 times higher than that of fasudil. Hydroxyfasudil may contribute to the potency of fasudil. The present findings indicate that the RKI fasudil reduces ischemic neuronal damage with a wide therapeutic time window in gerbil, and may be useful in the treatment of acute ischemic stroke in humans.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
0006-8993
pubmed:author
pubmed:issnType
Print
pubmed:day
12
pubmed:volume
1128
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
175-80
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Wide therapeutic time window for fasudil neuroprotection against ischemia-induced delayed neuronal death in gerbils.
pubmed:affiliation
Research Center, Asahi Kasei Pharma Corporation 632-1, Mifuku, Izunokuni-shi, Shizuoka 410-2321, Japan. sato.sn@om.asahi-kasei.co.jp
pubmed:publicationType
Journal Article