Journal Title
Title of Journal: Metab Brain Dis
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Abbravation: Metabolic Brain Disease
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Authors: Juan Bin Qian Wang YeYe Zhuo JiangPing Xu HanTing Zhang
Publish Date: 2012/07/29
Volume: 27, Issue: 4, Pages: 495-505
Abstract
The calcium sensitizers levosimendan and piperphentonamine hydrochloride PPTA are used as cardiovascular drugs for treatment of heart failure Given that levosimendan has been reported to exhibit a neuroprotective profile in a model of traumatic brain injury it was interesting to know whether PPTA a new calcium sensitizer recently developed in China exerts a similar effect The objective of this study was to determine whether PPTA exhibited neuroprotective effects and whether these properties were associated with memory Fourvessel occlusion 4VO was used to induce global cerebral ischemia/reperfusion injury in rats treated with or without PPTA 5 10 mg/kg ip 2 h after the onset of reperfusion and then once a day for 15 consecutive days Memory was measured using the stepthrough passive avoidance test Neurochemical changes were examined in rat PC12 cells treated with oxygenglucose deprivation OGD for 4 h followed by reoxygenation OGDR for 24 h in the absence or presence of PPTA In vehicletreated animals 4VO for 10 min produced memory deficits as demonstrated by decreased retention in stepthrough passive avoidance and massive neuron loss in the hippocampal CA1 subregion These effects were attenuated by PPTA The results were consistent with those observed in PC12 cells PPTA treatment increased cell viability as indicated by MTT assay inhibited apoptosis and decreased extracellular lactate dehydrogenase levels in Na2S2O4treated PC12 cells These results provide novel demonstration for the ability of PPTA to attenuate cerebral ischemiainduced memory deficits via neuroprotection in the hippocampus The neuroprotective effect of PPTA appears to be associated with its antiapoptotic activity PPTA has the therapeutic potential for ischemic stroke
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