Objective Our previous studies showed that the neuroprotective effect of pranlukast,a cysteinyl leukotriene receptor-1(CysLT1)antagonist,on global cerebral ischemia in rats.This study was performed to evaluate dose-an...Objective Our previous studies showed that the neuroprotective effect of pranlukast,a cysteinyl leukotriene receptor-1(CysLT1)antagonist,on global cerebral ischemia in rats.This study was performed to evaluate dose-and time-dependent properties of pranlukast on CA1 neuron loss following transient global ischemia in rats.Methods Brain injury was induced by an improved four-vessel occlusion(4-VO)in rats.pranlukast(0.03-0.30 mg·kg-1)was injected intraperitoneally either as multiple doses(before or after ischemia)or as a single dose(30 min before ischemia),respectively.Physiological variables were monitored and neuron count was measured by computer-assisted imaging.Results The 4-VO model produced continuing postischemic neuronal death in CA1 region.Administration of pranlukast(0.1 and 0.3 mg·kg-1,30 min before ischemia and 1,24,48 and 72 h after ischemia)markedly reduced CA1 death.Treatment with a single dose of pranlukast(0.1 mg·kg-1,30 min before ischemia)also resulted in a significant increase in the number of healthy CA1 neurons at 3 days.Of interest is the finding that pranlukast(0.1 mg·kg-1)rescued CA1 neurons from ischemic death even when treatment was delayed until 30 min or 1 h after ischemia.Conclusions The present study confirms pranlukast has a dose-and time-dependent cerebroprotective effects on CA1 neuron loss following transient global ischemia in rats,with an effective dose range of 0.1-0.3 mg·kg-1 and a therapeutic window of 1 h.These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of global cerebral ischemia.展开更多
AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral isch...AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO 1078 (0 01, 0 05, 0 10 mg·kg -1 ), dexamethasone (0 5 mg·kg -1 ), nimodipine (0 2 mg·kg -1 ) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS ONO 1078, dexamethasone and nimodipine reduced the neurological scores. ONO 1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO 1078 dose dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION ONO 1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.展开更多
文摘Objective Our previous studies showed that the neuroprotective effect of pranlukast,a cysteinyl leukotriene receptor-1(CysLT1)antagonist,on global cerebral ischemia in rats.This study was performed to evaluate dose-and time-dependent properties of pranlukast on CA1 neuron loss following transient global ischemia in rats.Methods Brain injury was induced by an improved four-vessel occlusion(4-VO)in rats.pranlukast(0.03-0.30 mg·kg-1)was injected intraperitoneally either as multiple doses(before or after ischemia)or as a single dose(30 min before ischemia),respectively.Physiological variables were monitored and neuron count was measured by computer-assisted imaging.Results The 4-VO model produced continuing postischemic neuronal death in CA1 region.Administration of pranlukast(0.1 and 0.3 mg·kg-1,30 min before ischemia and 1,24,48 and 72 h after ischemia)markedly reduced CA1 death.Treatment with a single dose of pranlukast(0.1 mg·kg-1,30 min before ischemia)also resulted in a significant increase in the number of healthy CA1 neurons at 3 days.Of interest is the finding that pranlukast(0.1 mg·kg-1)rescued CA1 neurons from ischemic death even when treatment was delayed until 30 min or 1 h after ischemia.Conclusions The present study confirms pranlukast has a dose-and time-dependent cerebroprotective effects on CA1 neuron loss following transient global ischemia in rats,with an effective dose range of 0.1-0.3 mg·kg-1 and a therapeutic window of 1 h.These findings further support the therapeutic potential of CysLT1 receptor antagonists in the treatment of global cerebral ischemia.
文摘AIM To determine whether ONO 1078 {pranlukast, 4 oxo 8 [p (4 phenylbutyloxy) benzoyl amino] 2 (tetrazol 5 yl) 4H 1 benzopyran hemihydrate}, a potent leukotriene antagonist, has protective effect on focal cerebral ischemia in mice. METHODS Focal cerebral ischemia was induced by permanent middle cerebral artery (MCA) occlusion in mice. ONO 1078 (0 01, 0 05, 0 10 mg·kg -1 ), dexamethasone (0 5 mg·kg -1 ), nimodipine (0 2 mg·kg -1 ) or saline (control) were injected ip once daily for 3 days, and 30 min before MCA occlusion. Twenty four hours after cerebral ischemia, the neurological scores were evaluated, infarct volumes and areas of the right and left cerebral hemispheres were measured by computer imaging analysis. RESULTS ONO 1078, dexamethasone and nimodipine reduced the neurological scores. ONO 1078 and dexamethasone reduced the ratio of right/left hemisphere area, indicating inhibition of brain edema, while nimodipine showed no effect. ONO 1078 dose dependently reduced infarct size, and dexamethasone and nimodipine showed the same effect. CONCLUSION ONO 1078 showed protective effect on focal cerebral ischemia. This may represent a novel approach to the treatment of acute cerebral ischemia.
