RT info:eu-repo/semantics/article
T1 LAU-0901, a novel platelet-activating factor antagonist, is highly neuroprotective in cerebral ischemia
A1 Belayev, Ludmila
A1 Khoutorova, Larissa
A1 Atkins, Kristal
A1 Gordon, William C.
A1 Álvarez-Builla Gómez, Julio
A1 Bazan, Nicolas G.
K1 LAU-0901
K1 PAF antagonist
K1 Middle cerebral artery occlusion
K1 Behavioral
K1 Histopathology
K1 Local cerebral blood flow
K1 Bioquímica
K1 Biochemistry
K1 Science
K1 Ciencia
AB 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.
PB Elsevier
SN 0014-4886
YR 2008
FD 2008
LK http://hdl.handle.net/10017/2674
UL http://hdl.handle.net/10017/2674
LA eng
NO NIH Grant NS23002 (NGB)
DS MINDS@UW
RD 26-abr-2024