Resveratrol suppressed seizures by attenuating IL-1, IL1-Ra, IL-6, and TNF- in the hippocampus and cortex of kindled mice

Resveratrol suppressed seizures by attenuating IL-1, IL1-Ra, IL-6, and TNF- in the hippocampus and cortex of kindled mice
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DOI:
10.1080/1028415x.2016.1189057
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发表时间:
2017-01-01
影响因子:
3.6
通讯作者:
Raisuddin, Sheikh
Raisuddin, Sheikh
中科院分区:
医学3区
文献类型:
--
作者:
Hoda, Ubedul;Agarwal, Nidhi Bharal;Raisuddin, Sheikh

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目的:由于目前可用的药物具有抗癫痫作用,并且三分之一的患者对该疾病仍然难治,因此迫切需要鉴定可以调节癫痫发生过程的新分子。方法:Swiss白化病小鼠经口给予白藜芦醇(Resveratrol,RESV)10、20和40 mg/kg,观察其对戊四氮(PTZ)点燃小鼠癫痫发生的影响。在第七天,对动物进行各种神经学和神经行为学测试,即,递增电流电休克测试(ICES)、PTZ诱导的癫痫发作、被动回避反应和高架十字迷宫测试。对于点燃的发展,每隔一天以25 mg/kg的剂量腹膜内给予PTZ,并且每天给予所有三个剂量的RESV。持续监测癫痫发作评分,直至研究结束时进行点燃和认知测试。将动物处死,并测定炎性生物标志物的水平,IL-1,白细胞介素-1受体拮抗剂(IL-1-Ra),IL-6,和TNF-α在点燃animals.Results的海马和皮层进行了评估:RESV在所有三个剂量增加癫痫发作阈值后肢延伸在ICES测试。结论:RESV能抑制小鼠点燃过程,降低海马组织炎症标志物的水平。RESV在癫痫发生过程中改变了脑炎症,并在点燃小鼠中发现具有促智活性。
Objective: There is an urge to identify new molecules which can modulate process of epileptogenesis, since currently available drugs act symptomatically and one-third of the patients remain refractory to the disease. Hence, the present study was conducted to evaluate the effects of Resveratrol (RESV) on epileptogenesis in pentylenetetrazole (PTZ)-induced kindling in mice.Method: Swiss albino mice were administered RESV (10, 20 and 40mg/kg,p.o) in acute study. On the seventh day animals were subjected to various neurological and neurobehavioral tests viz, Increasing Current Electroshock Test (ICES), PTZ-induced seizures, passive avoidance response, and elevated plus maze test. For the development of kindling PTZ was administered in a dose of 25mg/kg, i.p. on every alternate day and RESV in all the three doses was administered daily. Seizure score was continuously monitored till the development of kindling and cognition tests were performed in the end of the study. The animals were sacrificed and levels of inflammatory biomarkers viz., IL-1, interleukin-1 receptor antagonist (IL1-Ra), IL-6, and TNF- were assessed in the hippocampus and cortex of the kindled animals.Results: RESV in all three doses increased the seizure threshold to hind limb extension in the ICES test. RESV in all the tested doses suppressed the development of kindling and reduced the levels of IL-1, IL1-Ra, IL-6, and TNF- in kindled mice.Conclusion: RESV suppressed the development of kindling in mice and decreased the levels of inflammatory biomarkers in their hippocampus. RESV modified brain inflammation during epileptogenesis and found to possess nootropic activity in the kindled mice.