Effect of nordihydroguaiaretic acid on behavioral impairment and neuronal cell death after forebrain ischemia

The purpose of this study was to evaluate the neuroprotective effect of nordihydroguaiaretic acid (NDGA), an antioxidant and/or 5-lipoxygenase inhibitor, on ischemia–reperfusion injury behavioral pharmacologically and histologically in vivo. First, the antioxidant activity of NDGA was evaluated in vitro by measuring the production of thiobarbituric acid reactive substances (TBARS) in rat brain homogenate. Second, the effect of NDGA on learning and memory impairment induced by rat four-vessel occlusion transient ischemia was investigated with the Morris water-maze task. Third, the effect of NDGA on pyramidal cell loss in the hippocampus after transient ischemia was examined. NDGA inhibited the production of TBARS with an IC 50 of 0.1 μM, and significantly attenuated postischemic learning and memory impairment at 10 mg/kg. Furthermore, consecutive 4-day administration of NDGA at 10 mg/kg significantly reduced the postischemic neuronal death. NDGA was found to be potent and effective as an anti-ischemia–reperfusion injury agent in terms of behavioral pharmacology and histology. The present results suggest that NDGA has beneficial effects on behavioral deficits and histological injury caused by ischemia–reperfusion.