Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
2009-12-16
pubmed:abstractText
We investigated the neuroprotective effects of fasudil's active metabolite, hydroxyfasudil, a Rho-kinase inhibitor, in a rat stroke model in which endothelial damage and subsequent thrombotic occlusion were selectively induced in perforating arteries. By examining the effects on the endothelial damage/dysfunction, we thought to explore the mechanism of Rho-kinase inhibitors. Hydroxyfasudil (10mg/kg, i.p., once daily for 3 days) significantly improved neurological functions and reduced the size of the infarct area produced by internal carotid artery injection of sodium laurate in a rat cerebral microthrombosis model. Treatment with fasudil or hydroxyfasudil concentration-dependently inhibited tumor necrosis factor alpha-induced tissue factor expression on the surface of cultured human umbilical vein endothelial cells. They also inhibited thrombin-induced endothelial hyperpermeability. The present findings suggest that hydroxyfasudil is efficacious in preventing brain damage associated with cerebral ischemia, and is partially responsible for fasudil's cytoprotective potential. The results also suggest that the therapeutic benefits against ischemic injury of Rho-kinase inhibitors are attributed, at least in part, to activity upon endothelial damage/dysfunction.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jan
pubmed:issn
1873-2747
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
81
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
191-5
pubmed:meshHeading
pubmed-meshheading:19723568-1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine, pubmed-meshheading:19723568-Animals, pubmed-meshheading:19723568-Brain, pubmed-meshheading:19723568-Brain Ischemia, pubmed-meshheading:19723568-Capillary Permeability, pubmed-meshheading:19723568-Cells, Cultured, pubmed-meshheading:19723568-Disease Models, Animal, pubmed-meshheading:19723568-Endothelium, pubmed-meshheading:19723568-Enzyme Inhibitors, pubmed-meshheading:19723568-Humans, pubmed-meshheading:19723568-Male, pubmed-meshheading:19723568-Neuroprotective Agents, pubmed-meshheading:19723568-Rats, pubmed-meshheading:19723568-Rats, Sprague-Dawley, pubmed-meshheading:19723568-Stroke, pubmed-meshheading:19723568-Thromboplastin, pubmed-meshheading:19723568-Tumor Necrosis Factor-alpha, pubmed-meshheading:19723568-Umbilical Veins, pubmed-meshheading:19723568-rho-Associated Kinases
pubmed:year
2010
pubmed:articleTitle
Amelioration of endothelial damage/dysfunction is a possible mechanism for the neuroprotective effects of Rho-kinase inhibitors against ischemic brain damage.
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, In Vitro