Neuroprotective effect of ONO-1078, a leukotriene receptor antagonist, on focal cerebral ischemia in rats.
Abstract
AIM: To determine whether ONO-1078 (pranlukast), a potent leukotriene receptor
antagonist, has neuroprotective effect on focal cerebral ischemia in the rat.
METHODS: Focal cerebral ischemia was induced by 30 min of middle cerebral artery
(MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or
vehicle (saline 1 mL/kg) was ip injected 30 min before MCA occlusion and 2 h
after reperfusion. The neurological score, infarct volume, neuron density (in
cortex, hippocampus, and striatum), brain edema, and albumin exudation around the
vessels were determined 24 h after reperfusion.
RESULTS: ONO-1078 slightly improved the neurological deficiency, and dramatically
decreased infarct volume and neuron loss which showed a bell shaped dose response
effect with highest effect at doses of 0.01-0.3 mg/kg. Enlargement of the
ischemic hemisphere and albumin exudation were inhibited at doses of 0.01-1.0
mg/kg.
CONCLUSION: ONO-1078 has the protective effect on focal cerebral ischemia in
rats, which is partially attributed to the inhibition of brain edema. This may
represent a novel approach to the treatment of acute cerebral ischemia with
cysteinyl leukotriene receptor antagonists.
Keywords:
antagonist, has neuroprotective effect on focal cerebral ischemia in the rat.
METHODS: Focal cerebral ischemia was induced by 30 min of middle cerebral artery
(MCA) occlusion and followed by 24 h reperfusion. ONO-1078 (0.003-1.0 mg/kg) or
vehicle (saline 1 mL/kg) was ip injected 30 min before MCA occlusion and 2 h
after reperfusion. The neurological score, infarct volume, neuron density (in
cortex, hippocampus, and striatum), brain edema, and albumin exudation around the
vessels were determined 24 h after reperfusion.
RESULTS: ONO-1078 slightly improved the neurological deficiency, and dramatically
decreased infarct volume and neuron loss which showed a bell shaped dose response
effect with highest effect at doses of 0.01-0.3 mg/kg. Enlargement of the
ischemic hemisphere and albumin exudation were inhibited at doses of 0.01-1.0
mg/kg.
CONCLUSION: ONO-1078 has the protective effect on focal cerebral ischemia in
rats, which is partially attributed to the inhibition of brain edema. This may
represent a novel approach to the treatment of acute cerebral ischemia with
cysteinyl leukotriene receptor antagonists.