Diverse effects of variant doses of dexamethasone in lithium-pilocarpine induced seizures in rats
Diverse effects of variant doses of dexamethasone in lithium-pilocarpine induced seizures in rats
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DOI：
10.1139/y11-096
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发表时间：
2012-01-01
影响因子：
2.1
通讯作者：
Abdallah, Dalaal M.
中科院分区：
文献类型：
--
作者：
Al-Shorbagy, Muhammad Y.;El Sayeh, Bahia M.;Abdallah, Dalaal M.
皮质类固醇用于管理几种癫痫食物;然而，它们在对抗癫痫发作方面的有效性仍然存在争议，归因于促惊厥和抗惊厥作用。本研究旨在探讨地塞米松（DEX）在大鼠锂-匹罗卡品（Li-PIL）癫痫模型中的调节作用，采用3种剂量水平（5、10和20 mg/kg雄性Wistar大鼠体重）。Li-PIL诱导的癫痫发作与CA 3区域的神经元细胞丢失相关，并增加海马中的前列腺素（PG）E-2、肿瘤坏死因子（TNF）-α、白细胞介素（IL）-10、一氧化氮和中性粒细胞浸润。然而，Li-PIL损害了海马体的氧化-抗氧化平衡。仅在10 mg DEX/kg体重时观察到有效的抗惊厥活性，这降低了癫痫发作的产生和发生率，以及CA 3区域的神经元细胞丢失。在该抗惊厥剂量下，观察到抗氧化系统和IL-10的增强以及改变的炎症标志物的抑制。相反，剂量加倍显示出缩短癫痫发作潜伏期的趋势，既不影响癫痫发作发生率，也不影响CA 3神经元细胞丢失。这些作用与PGE（2）和TNF-α水平的增加有关。本研究发现，在Li-PIL癫痫模型中，5 mg DEX/kg体重时缺乏保护，10 mg/kg时具有抗惊厥作用，20 mg/kg时失去保护，这表明存在预防癫痫发作诱导的最佳DEX剂量。
Corticosteroids are used in the management of several epileptic aliments; however, their effectiveness in combating seizures remains controversial, with pro- and anti-convulsive effects ascribed. The current study aimed to address the modulatory effect of dexamethasone (DEX) utilizing 3 dose levels (5, 10, and 20 mg/kg body mass of male Wistar rat) in the rat lithium-pilocarpine (Li-PIL) epilepsy model. Li-PIL induced seizures that were associated with neuronal cell loss in the CA3 region, and increased prostaglandin (PG)E-2, tumor necrosis factor (TNF)-alpha, interleukin (IL)-10, nitric oxide, and neutrophil infiltration in the hippocampus. However, Li-PIL compromised the oxidant-antioxidant balance of the hippocampus. Effective anticonvulsant activity was only observed with10 mg DEX/kg body mass, which reduced seizure production and incidence, as well as neuronal cell loss in the CA3 region. At this anticonvulsant dose, enhancements in the antioxidant system and IL-10, as well as suppression of altered inflammatory markers were observed. Conversely, doubling the dose showed a tendency to shorten seizure latency, and neither affected seizure incidence nor CA3 neuronal cell loss. These effects were associated with an increase in levels of PGE(2) and TNF-alpha. The present study found a lack of protection at 5 mg DEX/kg body mass, an anticonvulsant effect at 10 mg/kg, and a loss of protection at 20 mg/kg in the Li-PIL epilepsy model, which indicates that there is an optimal dose of DEX for preventing the induction of seizures.