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姜黄素对戊四氮点燃癫痫大鼠模型发作和认知障碍的保护作用。

Protective effect of curcumin against seizures and cognitive impairment in a pentylenetetrazole-kindled epileptic rat model.

机构信息

Neuropharmacology Laboratory, Department of Pharmacology, All India Institute of Medical Sciences, New Delhi-110029, India.

出版信息

Life Sci. 2010 Nov 20;87(19-22):596-603. doi: 10.1016/j.lfs.2010.09.006. Epub 2010 Sep 16.

Abstract

AIM

Epilepsy as well as chronic use of most antiepileptic drugs predisposes to cognitive impairment. Curcumin has been reported to possess antioxidant, anticonvulsant as well as neuroprotective potential. Hence, this study was conducted to evaluate the effect of curcumin against seizures, cognitive impairment and oxidative stress in pentylenetetrazole-induced kindling in rats.

MAIN METHODS

The effect of pretreatment with curcumin (100, 200 and 300 mg/kg, orally) on pentylenetetrazole (PTZ)-induced kindling, kindling-induced cognitive impairment and oxidative stress was evaluated. Male Wistar rats were injected PTZ (30 mg/kg, i.p.) once every alternate day (48±1h) until the development of kindling. Cognitive impairment was assessed using elevated plus maze and passive avoidance test while the oxidative stress parameters (malondialdehyde and glutathione) were estimated in the whole brain at the end of experiments.

KEY FINDINGS

PTZ, 30 mg/kg, induced kindling in rats after 31.0±1.4 days. Curcumin showed dose-dependent anti-seizure effect. Curcumin (300 mg/kg) significantly increased the latency to myoclonic jerks, clonic seizures as well as generalized tonic-clonic seizures, improved the seizure score and decreased the number of myoclonic jerks. PTZ kindling induced a significant oxidative stress and cognitive impairment which was reversed by pretreatment with curcumin in a dose-dependent manner.

SIGNIFICANCE

The results indicate that pretreatment with curcumin ameliorates seizures, oxidative stress and cognitive impairment in PTZ induced kindling in rats. These results thus suggest the potential of curcumin as an adjuvant in epilepsy both to prevent seizures as well as to protect against seizure induced memory impairment.

摘要

目的

癫痫以及大多数抗癫痫药物的慢性使用会导致认知障碍。姜黄素具有抗氧化、抗惊厥和神经保护作用。因此,本研究旨在评估姜黄素对戊四氮诱导的大鼠点燃模型中的癫痫发作、认知障碍和氧化应激的影响。

主要方法

评价姜黄素(100、200 和 300mg/kg,口服)预处理对戊四氮(PTZ)诱导的点燃、点燃诱导的认知障碍和氧化应激的影响。雄性 Wistar 大鼠每隔一天(48±1h)腹腔注射 PTZ(30mg/kg),直到出现点燃。使用高架十字迷宫和被动回避测试评估认知障碍,而在实验结束时则在全脑评估氧化应激参数(丙二醛和谷胱甘肽)。

主要发现

PTZ,30mg/kg,在 31.0±1.4 天后诱导大鼠出现点燃。姜黄素表现出剂量依赖性的抗惊厥作用。姜黄素(300mg/kg)显著延长了肌阵挛性抽搐、阵挛性抽搐以及全身性强直阵挛性抽搐的潜伏期,改善了抽搐评分并减少了肌阵挛性抽搐的次数。PTZ 点燃导致氧化应激和认知障碍显著增加,而姜黄素预处理以剂量依赖性方式逆转了这些变化。

意义

结果表明,姜黄素预处理可改善 PTZ 诱导的大鼠点燃模型中的癫痫发作、氧化应激和认知障碍。这些结果表明,姜黄素具有作为抗癫痫药物的潜力,不仅可以预防癫痫发作,还可以防止癫痫发作引起的记忆障碍。

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