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脳虚血による空間記憶障害に対するPPARγ部分アゴニストとしてのテルミサルタンの作用
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JPY
Abstract
Telmisartan, an angiotensin receptor blocker(ARB), is used for hypertension in clinical stage and has been reported to have a partial agonistic effect on peroxisome proliferator-activated receptor(PPARγ). Recently, PPARγ related drugs have been implicated in neuroprotective effect due to their anti-inflammatory effects. In this study, we investigated whether telmisartan has a neuroprotective effect on memory impairment and neuronal cell death induced by repeated cerebral ischemia. Repeated cerebral ischemia(RI:10 min×2)significantly induced impairment of spatial memory and hippocampal apoptosis in rats. Fourteen days pre- and post-ischemic administration of telmisartan(0.3, 1, 3 mg/kg/day, p. o.)increased the number of correct choices and reduced the number of errors in the eight-arm radial maze task in RI treated rats. TUNEL-positive cells in the hippocampus CA1 areas were also reduced following 14 days-administration of telmisartan. Seven days post ischemic administration of telmisartan improved spatial memory and reduced TUNEL-positive apoptotic cells but not by 7 days pre-ischemic administration. These effects of telmisartan were inhibited by the PPARγ antagonist, GW9662. These results suggest that telmisartan improves memory impairment and reduces neuronal apoptosis via a PPARγ-dependent inhibiting mechanism. Telmisartan, which has the unique character of having both ARB and PPARγ agonistic effect, will be useful for preventing memory impairment after cerebrovascular disease.
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