Show simple item record

dc.contributor.authorBelayev, Ludmila
dc.contributor.authorKhoutorova, Larissa
dc.contributor.authorAtkins, Kristal
dc.contributor.authorGordon, William C.
dc.contributor.authorÁlvarez-Builla Gómez, Julio 
dc.contributor.authorBazan, Nicolas G.
dc.date.accessioned2009-04-29T11:35:07Z
dc.date.available2009-04-29T11:35:07Z
dc.date.issued2008
dc.identifier.bibliographicCitationExperimental Neurology, 2008, v.214, n.2, p.253-258en
dc.identifier.issn0014-4886
dc.identifier.urihttp://hdl.handle.net/10017/2674
dc.description.abstractPlatelet-activating factor (PAF) is a bioactive phospholipid that accumulates during ischemia-reperfusion and is involved in the activation of platelets, neutrophils, and pro-inflammatory signaling. PAF has been suggested to enhance brain ischemia-reperfusion damage. LAU-0901, a novel PAF receptor antagonist, was examined in models of focal cerebral ischemia in rats and mice. Sprague–Dawley rats were anesthetized and received 2-hour middle cerebral artery occlusion (MCAo) by intraluminal suture. LAU-0901 (30, 60, 90 mg/kg; n = 9–11) or vehicle (n = 11) was administered i.p. at 2 h after onset of MCAo. The neurological status was evaluated at 60 min, and on days 1, 2, 3 and 7 after MCAo. In the dose–response study in mice, C57BL/6 mice were anesthetized and received 1 h MCAo by intraluminal suture. LAU-0901 (15, 30, 60 mg/kg; n = 7–9) or vehicle (n = 8) was given i.p. at 1 h after onset of MCAo. Local cerebral blood flow (LCBF) was measured at 1, 2, 4, and 6 h after MCAo in mice. LAU-0901 treated rats showed improved neurological score throughout the 7-day survival period. LAU-0901 treatment (30, 60 and 90 mg/kg) reduced total corrected infarct volume compared to vehicle rats by 76, 88 and 90%, respectively. Mice treated with LAU-0901 (30 and 60 mg/kg) reduced total infarction by 29% and 66%, respectively. LCBF was improved by treatment with LAU-0901 (30 mg/kg) by 77% of baseline at 6 h. In conclusion, we demonstrate for the first time that LAU-0901 improves behavioral scores, LCBF and reduces infarct volume after focal cerebral ischemia in rats and mice. Thus, this PAF receptor antagonist exhibits potent and sustained neuroprotection that may be of value for the design of stroke therapies.en
dc.description.sponsorshipNIH Grant NS23002 (NGB)en
dc.format.mimetypeapplication/pdfen
dc.language.isoengen
dc.publisherElsevieren
dc.rights© Elsevier, 2008
dc.subjectLAU-0901en
dc.subjectPAF antagonisten
dc.subjectMiddle cerebral artery occlusionen
dc.subjectBehavioralen
dc.subjectHistopathologyen
dc.subjectLocal cerebral blood flowen
dc.titleLAU-0901, a novel platelet-activating factor antagonist, is highly neuroprotective in cerebral ischemiaen
dc.typeinfo:eu-repo/semantics/articleen
dc.subject.ecienciaBioquímicaes_ES
dc.subject.ecienciaBiochemistryen
dc.subject.ecienciaScienceen
dc.subject.ecienciaCienciaes_ES
dc.contributor.affiliationUniversidad de Alcalá. Departamento de Química Orgánica
dc.relation.publisherversionhttp://dx.doi.org/10.1016/j.expneurol.2008.08.009
dc.type.versioninfo:eu-repo/semantics/publishedVersionen
dc.identifier.doi10.1016/j.expneurol.2008.08.009
dc.rights.accessRightsinfo:eu-repo/semantics/openAccessen


Files in this item

Thumbnail

This item appears in the following Collection(s)