戊四氮点燃癫痫大鼠空间学习记忆障碍及海马突触素表达减少的研究

目的:探讨戊四氮点燃癫痫对大鼠空间学习记忆的影响及可能的分子机制。方法:戊四氮(pentylenetet-razol,PTZ)点燃建立慢性癫痫(chronic epileptic,CEP)模型,Morris水迷宫进行行为学检测,western blot方法观察大鼠海马突触素(synaptophysin,P38)蛋白的表达变化。结果:水迷宫试验检测癫痫组大鼠空间学习记忆能力受损(P<0.05,P<0.01);western blot结果表明海马P38蛋白表达较对照组明显减少(P<0.05)。结论:戊四氮点燃癫痫大鼠伴有学习记忆功能减退,其海马P38蛋白的表达减少可能参与了空间学习记忆受损。     

SB-271046对匹罗卡品致痫大鼠空间学习记忆的影响

目的观察5-羟色胺6受体拮抗剂SB-271046对匹罗卡品致痫大鼠空间学习记忆的作用效应。方法成年雄性SD大鼠分为两组:空白对照组(Vehicle组,n=10),氯化锂-匹罗卡品组(Lithium chloride-Pilocarpine,LiCl-PILO组,n=40)。首先根据注射LiCl-PILO后是否出现癫痫持续状态(Status Epilepticus,SE),出现SE者纳入实验,未出现SE和死亡者则剔除;然后再随机分为3组:模型组即侧脑室注射羟丙基-β-环糊精(Hydroxypropyl-β-cyclodextrine,HP-β-CD),4μl;药物组按不同剂量分为2组,即侧脑室注射N-[4-Methoxy-3-(4-methyl-1-piperazinyl)-phenyl]-5-chloro-3-methylbenzo-thiophene-2-yl-sulphonamide monohydrochloride(SB-271047)剂量为10μg,4μl和侧脑室注射SB-271046剂量为20μg,4μl。结果在Y迷宫自主交替行为实验中,模型组自主交替率显著下降(P0.01),药物组显著提高尤其是20μg剂量组(P0.05)。在Y迷宫新奇事物探索实验中,模型组的新臂时间比显著下降(P0.01),药物组有提高趋势(P0.05)。在Morris水迷宫定位航行实验中,模型组平均潜伏期延长显著延长(P0.01),药物组明显缩短尤其是20μg剂量组(P0.05)。在Morris水迷宫空间探索实验中,模型组平均潜伏期延长,穿越平台次数减少,原平台象限停留时间缩短(P0.05),药物组有改善趋势(P0.05)。结论 SB-271046可以改善癫痫大鼠的空间学习记忆,主要作用于记忆获得巩固阶段,20μg剂量作用明显。     

戊四氮致痫大鼠学习记忆改变及海马CA_1和CA_3区神经颗粒素的表达变化

目的 探讨戊四氮慢性点燃癫痫对大鼠学习记忆能力的影响及海马CA_1、CA_3区神经颗粒素(neu-rogranin,Ng)的表达变化.方法 采用戊四氮(pentylenetetrazole,PTZ)腹腔注射慢性点燃癫痫(chronic epileptic,CEP)模型,用Morris水迷宫和Y迷宫对大鼠进行学习记忆能力检测,运用免疫组织化学方法测定大鼠海马CA_1、CA_3区Ng的表达变化.结果 与对照组比较,慢性癫痫发作组大鼠在水迷宫中的逃避潜伏期延长(P<0.01),穿越平台次数减少(P<0.01),在Y迷宫中的错误反应次数增多(P<0.05).在海马CA_1区Ng的免疫反应强度减弱(P<0.05),CA_3区两组比较差异无统计学意义.结论 戊四氮慢性点燃癫痫大鼠学习记忆能力受损,海马CA_1区Ng表达减少可能参与了这一过程.

Abstract：

Objective To explore the effect of Pentylenetetrazole (PTZ)-kindled epilepsy on rats' learning and memory and the expression of neurogranin(Ng) in hippocampal CA_1 and CA_3. Methods Use chronic model of epilepsy induced by PTZ intraperitoneal injection. The ability of learning and memory were assessed by the Morris water maze and Y maze. The expression of Ng in hippocampal CA_1 and CA_3 was determined by immunocytochemical method respectively. Resuits The learning and memory ability of the epilepsy rats was impaired. Meanwhile,The immunological reaction of Ng for CEP group at CA_1 was weaker than NC group, but it made no difference at CA_3. Conclusion The impairment of learning and memory ability of the epilepsy rats might be related with the changes of Ng in hippocampal CA_1.     

白藜芦醇对戊四氮致痫大鼠的学习记忆能力的影响

目的 研究白藜芦醇对戊四氮致痫大鼠的空间学习记忆能力的影响.方法 采用戊四氮亚惊厥剂量腹腔注射建立慢性癫痫模型,造模成功后予以白藜芦醇15 mg/kg灌胃干预10 d,行Morris 水迷宫实验测试大鼠的空间学习和记忆能力.结果 经28 d连续给药,18只大鼠符合Racine点燃标准,Res干预组大鼠痫性发作潜伏期明显延长,且其发作时间明显低于癫痫模型组、二甲基亚砜组,差异有统计学意义(P＜0.05).定位航行试验:实验第1、2d,各组大鼠逃避潜伏期差异没有统计学意义,而第3、4、5d癫痫模型组、二甲基亚砜组大鼠逃避潜伏期比正常对照组明显延长,Res干预组大鼠逃避潜伏期明显低于癫痫模型组、二甲基亚砜组,差异有统计学意义(P＜0.05).空间探索试验:将原站台撤去后,癫痫模型组、二甲基亚砜组穿越原站台次数和象限逗留时间,比正常对照组明显减少;同Res干预组相比减少,差异有统计学意义(P＜0.05).结论 白藜芦醇对戊四氮致痫大鼠具有抗癫痫和改善其空间学习记忆能力.     

低剂量伽玛刀照射对癫痫模型大鼠癫痫发作及认知功能的影响

目的观察低剂量伽玛刀照射对癫痫大鼠的抗癫痫作用及对认知功能的影响。方法根据动物是否致痫及接受伽玛刀照射,将60只大鼠分为4组:①正常对照组;②伽玛刀对照组;③戊四氮(pentylenetetrazole,PTZ)组;④PTZ+伽玛刀组。腹腔连续注射PTZ制备癫痫大鼠模型,以双侧额叶为照射靶区对大鼠进行低剂量伽玛刀照射,边缘剂量为15Gy。观察并记录各组大鼠伽玛刀照射前、后的癫痫发作情况及脑电图变化,并于伽玛刀照射后12周,应用Morris水迷宫评测各组大鼠学习和记忆功能。结果与PTZ组大鼠比较,PTZ+伽玛刀组大鼠经低剂量伽玛刀照射后,于8～12周时,发作程度明显减轻,癫痫波发放的潜伏期延长,频率显著减少(P0.05)。在Morris水迷宫试验中,与正常对照组比较,PTZ组大鼠搜索策略变差,寻找平台逃避潜伏期时间显著延长,游泳距离增加,穿越平台的次数及在原平台象限的游泳时间的百分率减少(P0.05);而与PTZ组相比,PTZ+伽玛刀组搜索策略明显改善,寻找平台逃避潜伏期时间缩短,游泳距离减少,穿越平台的次数及在原平台象限的游泳时间的百分率明显增加(P0.05)。结论 PTZ致痫大鼠认知功能明显受损,低剂量伽玛刀照射在控制大鼠癫痫发作的同时,可改善认知功能。     

癫痫持续状态对发育期大鼠认知功能的影响及cAMP/PKA信号通路所起作用

目的 探讨癫痫持续状态(SE)对发育期大鼠认知功能的影响及环磷酸腺苷/蛋白激酶A(cAMP/PKA)信号转导通路在其中所起的作用.方法 SD大鼠32只按照完全随机数字表法分为SE组、生理盐水(NS)组,每组16只.戊四氮(PTZ)诱导大鼠SE,Morris水迷宫和Y迷宫实验观察大鼠学习记忆功能的改变,放射免疫分析法测定海马组织cAMP的含量,免疫组织化学方法检测海马各区PKA的表达.结果 SE组大鼠在Morris水迷宫中平均逃避潜伏期延长,原平台所在象限的游泳时间缩短,与NS组比较差异有统计学意义(P<0.05).在Y迷宫中达标所需的训练次数增多,24 h记忆保持率下降,与NS组比较差异有统计学意义(P<0.05).NS组大鼠海马cAMP的含量为(280.38±22.66)pmol/g,SE组为(147.25±16.83)pmol/g,差异有统计学意义(P<0.05).SE组CA3区和CA1区PKA的表达较NS组明显减少.结论 SE可以导致发育期大鼠认知功能障碍,其机制可能与cAMP/PKA信号转导通路的功能受损有关.

Abstract：

Objective To observe the influence of status epilepticus (SE) on cognitive function of immature rats and explore the role of hippocampal cAMP/PKA signaling pathway in cognitive function impairment of immature rats. Methods Immature male SD rats were assigned randomly to 2 groups: SE group, induced by intraperitoneal injection of pentylenetetrazole (PTZ, n=16), and normal saline control group (n=16). Learning and memory tests using the Morris water maze and Y-maze were performed 7 d after SE. After testing, alterations of content of cAMP were detected by radioimmunoassay,and the expression of PKA in the hippocampus was examined by immunohistochemistry. Results SE rats exhibited learning and memory deficits in the Morris water maze and Y-maze tests: as compared with those in the controls in Morris water maze, the mean escape latency of searching the platform obviously prolonged and the swimming time in the original platform region significantly shortened in SE rats (P<0.05); as compared with those in the controls in Y maze, the number of standard training times obviously increased and the rate of retention of memory significantly decreased in SE rats (P<0.05). At the same time, the cAMP content in hippocampus of SE rats ([147.25±16.83] pmol/g) was significantly lower as compared with that in controls ([280.38±22.66] pmol/g), and the expression of PKA in the CA3 and CA1 areas within hippocampal area of SE rats was obviously decreased as compared with that in controls (P<0.05). Conclusion SE could result in learning and memory deficits in immature rats, which may be related to the impairment of hippocampal cAMP/PKA signaling pathway.     

雷公藤多甙对致痫大鼠学习记忆及海马Ng和PKC表达的影响

目的研究雷公藤多甙(TWP)在戊四氮(PTZ)所致癫痫大鼠学习记忆障碍中的干预作用及可能机制,探讨神经颗粒素(Ng)和蛋白激酶C(PKC)在癫痫大鼠海马组织中的表达的影响。方法通过水迷宫及Y迷宫筛选方式挑选学习记忆功能正常的SD大鼠90只,随机分为PTZ致痫组、TWP低剂量组(TWP1)、TWP高剂量组(TWP2)、正常对照组,采用戊四氮(PTZ)腹腔注射慢性点燃癫痫。用水迷宫和Y迷宫对4组大鼠进行学习记忆能力检测,运用实时荧光定量PCR及酶联免疫吸附法分别检测其海马组织Ng和PKC基因mRNA及相应蛋白的表达水平。结果与PTZ组相比,TWP干预组大鼠在水迷宫中提高,其学习记忆能力接近NC组(P0.05);而4组逃避潜伏期差异无统计学意义(P0.05)。在Y迷宫TWP干预组错误反应次数比PTZ组明显减少(P0.05),其行为能力接近NC组(P0.05);但4组在全天总反应时间上的差异无统计学意义(P0.05)。经TWP干预后大鼠海马Ng和PKC基因mRNA及相应蛋白的表达上调,与PTZ组比较,差异具有统计学意义(P0.05),上调水平与NC组接近(P0.05);而TWP1和TWP2两组之间的差异无统计学意义(P0.05)。结论 TWP可有效改善PTZ所致癫痫大鼠的学习记忆能力,这与上调大鼠海马组织Ng及PKC表达水平密切相关。     

虾青素对致痫大鼠学习记忆能力的影响及机制探讨

目的观察虾青素(ASX)对杏仁核电点燃癫痫大鼠模型学习记忆能力的改善作用,并检测海马氧化应激和凋亡指标以探讨其作用机制。方法选取雄性成年SD大鼠,随机分为:对照组、癫痫组、高剂量ASX组(30mg·kg~(-1))、低剂量ASX组(15mg·kg~(-1))4组,每组15只。对照组仅给予电极植入,其余3组制备杏仁核慢性电点燃癫痫模型。ASX干预组分别于每天电刺激前1h给予ASX腹腔注射。在最后1次电刺激24h后行Morris水迷宫实验观察致痫大鼠学习记忆能力,检测各组大鼠海马组织中氧化应激参数的含量及凋亡参数蛋白表达水平。结果①Morris水迷宫实验:定位航行实验的1～5d,低剂量和高剂量ASX组的逃避潜伏期较癫痫组均明显缩短(~均P0.05),在空间探索实验中,低剂量和高剂量ASX组穿越平台次数较癫痫组均明显增多(~均P0.05);②海马氧化应激参数:低剂量和高剂量ASX组与癫痫组比较,丙二醛(MDA)含量均明显降低(~均P0.05),而谷胱甘肽(GSH)均明显升高(~均P0.05);③海马凋亡参数:低剂量和高剂量ASX组与癫痫组比较,Bcl-2蛋白表达水平均明显升高(~均P0.05),而Bax蛋白表达水平均明显降低(~均P0.05)。结论 ASX能够明显改善致痫大鼠的学习记忆能力,其机制与抗氧化及抗凋亡作用有关。     

大鼠癫痫持续状态后认知功能变化模式及海马脑红蛋白表达水平的实验研究

目的观察大鼠癫痫持续状态(SE)后学习记忆功能改变情况及海马组织脑红蛋白(NGB)表达水平,探讨癫痫发作对认知功能影响的可能机制。方法健康成年雄性SD大鼠40只,随机分为对照组(n=5)、癫痫模型实验组(n=35),模型组再依据观察时间分为:0 h、1 h、3 h、12 h、24 h、10 d、30 d。应用氯化锂-匹罗卡品(Li-Pilo)建立SE模型,观察致痫期间大鼠行为学变化;采用Nissl染色检测神经元损伤情况;SABC免疫组化法检测NGB表达水平。同时随机选取同期相同品系SD大鼠40只,在造模前及造模后第5d、10 d、15 d、25 d、35 d进行RMT-100迷宫实验,以评价大鼠SE前后学习记忆功能变化情况。结果大鼠SE后,海马CA1、CA3区和DG区均出现不同程度神经元细胞损伤坏死,且NGB表达上调,而海马CA1和CA3区神经元存活数与NGB表达水平呈正相关(r=0.206,P=0.015;r=0.306,P=0.011)。迷宫实验显示工作记忆错误(WME)和参照记忆错误(RME)次数随SE后时间延长均呈递增趋势。相关性分析证实RME次数与CA1和CA3区神经元存活数呈负相关(r=-0.579,P=0.000;r=-0.454,P=0.002),WME次数与CA1和CA3区神经元存活数也呈负相关(r=-0.470,P=0.001;r=-0.507,P=0.000)。结论 SE后NGB表达上调,且与海马组织神经元存活数呈正相关,提示其可能是SE所致缺血缺氧损害的一种代偿神经保护机制。SE后可导致明显认知功能损害,其可能与SE所致海马组织神经元的病理改变相关。     

甲硫氨酸维B_1对创伤性癫痫大鼠的治疗机制研究

目的探讨甲硫氨酸维B_1(MVB_1)对创伤性癫痫(PTE)的治疗机制。方法将15只雄性SD大鼠随机分为假手术组、癫痫组和癫痫MVB1治疗组,Morris水迷宫方法观察各组大鼠学习和记忆行为变化,检测各组大鼠血清和海马组织中超氧化物歧化酶(SOD)、丙二醛(MDA)和还原性谷胱甘肽(GSH)浓度变化。结果癫痫组大鼠5d的逃避潜伏期显著延长,站台穿越次数显著降低,目标象限时间显著缩短,血清及海马组织SOD和GSH水平显著降低,MDA水平显著增加。癫痫大鼠MVB1处理后,5d的逃避潜伏期均显著缩短,站台穿越次数显著增加,目标象限时间显著延长,血清及海马组织SOD和GSH水平显著增加,MDA水平显著降低。结论 MVB1可改善PTE大鼠的学习记忆功能,可通过提高SOD和GSH浓度,降低MDA浓度来抑制脂质过氧化和减轻自由基损伤,为MVB1临床治疗癫痫提供了新的理论依据。     

化学点燃癫痫大鼠在水迷宫中学习记忆能力的测定

目的 观察印防己毒（Picrotoxin,PTX)化学点燃癫痫大鼠在水迷宫中学习记忆能力与发作频率及类型的关系。为进一步研究癫痫患者记忆损害的治疗提供线索。方法 34只雄性SD大鼠随机分为点燃组和对照组。分别用PTX和生理盐水腹腔注射，根据点燃情况点燃组再分为全面发作（A），频繁发作（B）和部分发作（C）组，对照组即为迷宫训练（D）组。然后进行水迷宫行为测试，评价其学习记忆能力。结果 癫痫大鼠在水迷宫测定中，除B组第1天的成绩较对照组差外，其余各组及B组在第2，3，4、5天中寻找平台的潜伏期时间与对照组相比没有显著性差异。点燃各组对平台空间位置的记忆能力较对照组要差。差异有显著性。结论 首次用化学点燃模型研究癫痫大鼠在水迷宫中的学习记忆能力后发现。PTX化学点燃癫痫大鼠在水迷宫中学习记忆能力下降。发作频繁者学习记忆受损明显，但与发作的严重程度无关。     

Consequences of Pentylenetetrazole Kindling on Spatial Memory and Emotional Responding in the Rat

We investigated the consequences of pentylenetetrazole (PTZ) kindling on cognitive capacities of rats in a Morris water maze assessing spatial reference memory and in the spontaneous alternation test used as an index of working memory. The emotional consequences of PTZ kindling were also evaluated in an elevated plus maze test. Results indicated that PTZ kindled rats were not different from controls in mastering the water maze. However, PTZ kindled rats did not persist in searching the platform when evaluated at the end of learning. This suggests an altered place memory, although alternative explanations, like reduced anxiety, may be involved. Indeed, such anxiolytic activity was observed in a separate group of kindled rats evaluated in the plus maze test. No significant effect of PTZ kindling was noted in the spontaneous alternation test. These results question the generalization of previous results obtained in learning tests using electric shocks and illustrate the complexity of the PTZ model for the study of the behavioral consequences of kindling.     

Differential Impairments of Spatial Memory and Social Behavior in Two Models of Limbic Epilepsy

Summary: To explore memory impairments in temporal lobe epilepsy, we used two experimental models in the rats: (a) kainate-induced status epilepticus (SE) resulting in excitotoxic damage and in later spontaneous seizures; and (b) amygdala kindling, known to induce no lesions (or only minor) and neuronal reorganization. Long-term effects of these models on memory were investigated with a spatial learning task in a radial-arm maze, and a social interaction test that implies degree of short-term memory. An histological analysis was made to determine neuronal damage or loss caused by epileptic activity in brain regions that could be related to memory functions. Kainate-induced epilepsy produced large memory deficits in animals tested 5 months after the injection. The rats showed severe lesions in amygdala and hippocampus and piriform and entorhinal cortex. Spatial memory was strongly diminished. The social memory test was severely impaired, probably due to the extent of amygdala injury, which is known to disturb social behavior. On the contrary, kindled rats showed no evident lesion in any brain region and displayed performances as good as those of controls in both tests. These experiments demonstrated that memory deficits appear to be related to the severity of neuronal damage in limbic areas, and the ability to develop seizures (permanence) is not solely responsible for these memory disturbances.     

Effects of glutamine pretreatment on learning and memory in heat-exposed rats

BACKGROUND： Glutamine （Gin） pretreatment can protect neural cells from injuries due to heat, ischemia, hypoxia, endotoxemia, and inflammatory factors. OBJECTIVE： To observe the effects of Gin pretreatment on learning and memory, survival time, and rectal temperature in heat-exposed rats. DESIGN, TIME AND SETTING： The present randomized grouping, neurobehavioral experiment was performed at the Laboratory of Department of Pharmacology, Basic School of Medicine, Wuhan University between March and September 2007. MATERIALS： Twenty-four healthy, Wistar rats were included in this study. SPX-160B biochemistry incubator （Shanghai Experimental Equipment Co., Ltd., China）, probe electronic thermometer （11000 type, Maikepai Science and Technology Co., Ltd., China）, Y-type maze box used in conjunction with MG-2 maze stimulator （Zhangjiagang Biomedical Instrument Factory, China）, L-Gln （Batch No. 061218, 5 g/bottle, prepared into 10% aqueous solution, Amresco Company, USA） were used. METHODS： Twenty-four rats were randomly and evenly divided into 3 groups： heat-exposed, Gln low-lose, and Gln high-dose. Following learning and memory testing with the Y-maze, rats in the heat-exposed group were subjected to heat injury （40.5-41.5 ℃） in a biochemistry incubator. Rectal temperature was measured every 5 minutes. Thirty-five minutes after heat exposure, rats were removed and placed in the Y-type maze to test learning and memory again. Subsequently, the rats were returned to the same environment of thermal stimulation until they died. Rat survival time was recorded. Subsequent to learning and memory testing, rats in the Gin low-dose and high-dose groups received an i.p. injection of Gin （0.4 g/kg and 0.8 g/kg, respectively）, and were exposed to heat injury. The remaining experimental procedures remained the same as for the heat-exposed group. MAIN OUTCOME MEASURES： Rat learning and memory, rectal temperature, and survival time in heat exposure environment. RESULTS： （1） In the Y-maze e     

Alteraciones del metabolismo oxidativo y de la memoria y el aprendizaje en un modelo de hipoperfusión cerebral en ratas

Introduction

Chronic hypoperfusion in rats produces memory and learning impairments due to permanent occlusion of commun carotid arteries (POCCA). Molecular mechanisms leading to behavioural disorders have been poorly studied. For this reason, the aim of the present study was to characterise oxidative metabolism disorders and their implications in memory and learning impairments.

Methods

Superoxide dismutase (SOD) and catalase (CAT) activities were determined in cortex, hippocampus and striatum homogenates at 24 hours and at 22 days after the lesion. Haematoxylin-eosin staining and glial fibrillary acidic protein (GFAP) immunoreactivity were performed on coronal sections. Behavioural impairments were explored using the Morris water maze (MWM). Escape latencies were determined in all behavioural studies.

Results

The lesion induced a significant increase (P<.01) in CAT activity in the cortex at 24 hours, while SOD activity was significantly higher (P<.01) in the cortex and hippocampus at 22 days. An intense vacuolization was observed in the cortex and striatum as a result of the lesion. A neuronal loss in the striatum and hippocampus was observed. The glial reaction increased in the cortex and striatum. Visual alterations were observed in the lesion group with the lowest evolution time (P<.001). Escape latencies, corresponding to MWM schemes for long-term and short-term memory evaluation increased significantly (P<.05) in both groups of lesioned animals.

Conclusion

It was concluded that changes in SOD and CAT activities indicate a possible implication of oxidative imbalance in the pathology associated with chronic cerebral hypoperfusion. In addition, the POCCA model in rats is useful for understanding mechanisms by which cerebral hypoperfusion produces memory and learning impairments.     

马桑内酯点燃癫(癎)大鼠海马及齿状回区CGRP变化的初步研究

目的了解马桑内酯(CL)点燃癫大鼠海马及齿状回降钙素基因相关肽(CGRP)表达变化,探讨其可能的作用及机理。方法健康雄性SD大鼠30只,随机分为2组:对照组(C组,n=6)和实验组(n=24)。实验组肌肉注射CL0.20ml/kg,次/60h,平均20次;24h内有3~5级(Racinescale)性发作,或连续2次注射期间发作10次或以上为点燃(K组),否则为未点燃(NK组);C组注射等量生理盐水。取各组脑组织行CGRP免疫组化染色,应用Image-proplus4.5图像分析系统检测其变化。结果11只大鼠点燃成功,K组CGRP表达较NK组和C组显著增强(P<0.05)。结论CL点燃癫诱发大鼠海马及齿状回CGRP表达明显增强,CGRP可能在CL点燃癫中发挥一定的作用。     

Anticonvulsant activity of the cyclooxygenase-2 (COX-2) inhibitor etoricoxib in pentylenetetrazole-kindled rats is associated with memory impairment

PurposeVarious selective and nonselective cyclooxygenase (COX) inhibitors are known to have effects on development and progression of seizures. In the present study, the effect of the selective COX-2 inhibitor etoricoxib on seizures, oxidative stress, and learning and memory was studied.MethodMale Wistar rats were kindled using subconvulsant dose of pentylenetetrazole (PTZ) (30 mg/kg, i.p.), on alternating days until animals were fully kindled. After a one-week PTZ-free period, kindled rats were challenged with PTZ 30 mg/kg, and the latency, duration, and severity of seizures were recorded. Etoricoxib was then administered intraperitoneally at 1 mg/kg and 10 mg/kg in kindled rats for nine days (days 6–14). On the ninth day of etoricoxib treatment, PTZ challenge (30 mg/kg) was given, and seizure parameters were noted. On day 15, behavioral assessment was carried out. The Morris water maze (MWM) apparatus and the passive avoidance (PA) apparatus were used for studying cognitive impairment. The rats were then sacrificed, and malondialdehyde (MDA) and glutathione (GSH), markers of oxidative stress, were estimated in the brain samples.ResultsEtoricoxib at lower dose (1 mg/kg) had an anticonvulsant effect which was reduced or reversed at higher dose (10 mg/kg). Etoricoxib also impaired the learning and memory in rats as tested by passive avoidance and Morris water maze tests.ConclusionThe results of the present study suggest that use of etoricoxib, especially at low dose, in patients with epilepsy may not be detrimental with regard to seizure control. However, attention should be paid to cognitive parameters.