FR128998 (a PAF receptor antagonist) counters the increased pulmonary vascular resistance associated with ischemia-reperfusion injury in the canine lung

Iwazaki, Shigeru; Izumi, Tohru; Ohwada, Susumu; Saito, Yutaka; Aiba, Motohiko; Tsutsumi, Hirofumi; Kawashima, Yasunaru; Matsumoto, Koshi; Morishita, Yasuo

doi:10.1055/s-0031-1276270

Cited by 1 publication

(1 citation statement)

References 15 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…PAF antagonists, after ischemia and reperfusion, has been shown to be beneficial in different animal models: myocardial reperfusion injury in swine (Loucks et al, 2000), lung ischemia-reperfusion injury in canine (Iwazaki et al, 2001), intestinal ischemia-reperfusion in mouse (Souza et al, 2003), acute hepatic injury in rat (Grypioti et al, 2008) and renal ischemia in rat (Lloberas et al, 2001). …”

Section: Discussionmentioning

confidence: 99%

LAU-0901, a novel platelet-activating factor antagonist, is highly neuroprotective in cerebral ischemia

Belayev

Khoutorova

Atkins

et al. 2008

Experimental Neurology

View full text Add to dashboard Cite

Middle cerebral artery occlusion Behavioral Histopathology Local cerebral blood flow Platelet-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.

show abstract

Section: Discussionmentioning

confidence: 99%