L—NAME促进大鼠红藻氨酸诱导性发作

为证明癫痫发作早期一氧化氮（ＮＯ）抗发作效应，用ＮＯ合酶（ＮＯＳ）抑制剂Ｌ－硝基精氨酸甲酯（Ｌ－ＮＡＭＥ）对大鼠红藻氨酸（ＫＡ）诱导性发作进行干预，同时用分光光度法检测海马结构中ＮＯＳ活性的早期变化。发现ＫＡ发作１０ｍｉｎ、３０ｍｉｎ组海马结构中ＮＯＳ活性明显升高，而ＫＡ注射前３０ｍｉｎ给予Ｌ－ＮＡＭＥ可显著抑制ＮＯＳ活性的升高，这种抑制效应与大鼠ＫＡ发作中湿狗样摇动（ＷＤＳ）的提早出现和发生次数增多显著相关。结果提示在ＫＡ诱导大鼠发作早期内源性ＮＯ具有明显的抗发作效用。     

海人酸致痫动物模型脑内一氧化氮,一氧化氮合酶的变化

目的探讨一氧化氮（ＮＯ）、一氧化氮合酶（ＮＯＳ）在癫痫发生中的作用及ＮＯＳ抑制剂的作用。方法采用海人酸致痫大鼠模型并应用ＮＯＳ抑制剂Ｌ－硝基精氨酸甲酯（Ｌ－ＮＡＭＥ）,分别在致痫后３０分钟、６０分钟取海马组织,匀浆后测定ＮＯ及ＮＯＳ水平。结果致痫３０分钟后海马ＮＯ含量显著升高,至６０分钟恢复正常;ＮＯＳ活性水平增高＞５０％;Ｌ－ＮＡＭＥ明显抑制大鼠的痫性发作,应用ＮＯＳ抑制剂组大鼠海马ＮＯ、ＮＯＳ含量明显下降。结论癫痫发作后脑内ＮＯ、ＮＯＳ活性增强,ＮＯＳ抑制剂通过抑制酶活性使ＮＯ生成降低,并完全抑制痫性发作。ＮＯＳ活性受抑制＞４８％即可产生明显效果。提示ＮＯ可能有内源性致痫作用。     

红藻氨酸诱导癫痫发作小鼠脑组织中 NO_2~- 与硫代巴比妥酸反应物浓度测定

了解活性介质一氧化氮（ＮＯ）与癫痫发作的关系。方法用比色法检测红藻氨酸（ＫＡ）诱导ＢＡＬＢ／ｃ小鼠癫痫发作后，不同时点脑匀浆上清液中亚硝酸根（ＮＯ２－）与硫代巴比妥酸（ＴＢＡ）反应物的含量。结果ＮＯ２－浓度与ＴＢＡ反应物含量的多少与ＫＡ诱导的癫痫发作时程有关。在发作初期，ＮＯ２－随发作持续而增多，但发作后期又迅速减少。ＮＯ２－浓度的升高与减低受Ｌ－精氨酸（Ｌ－Ａｒｇ）及其硝基衍生物ＮＧ位硝基左型精氨酸（Ｌ－ＮＮＡ）的影响。同时对ＮＯ２－检测标本做ＴＢＡ反应物检测，发现ＮＯ２－的减少与ＴＢＡ反应物增多相关，在癫痫发作初期ＴＢＡ反应物含量较低，但随着发作时间的延长明显增多，ＴＢＡ含量的变化同样可受Ｌ－Ａｒｇ与Ｌ－ＮＮＡ的影响。结论Ｌ－Ａｒｇ－ＮＯ途径可能参与了癫痫发作的起动、传播和继发性脑损害的全过程，在发作后期，过量生成的ＮＯ可能有神经兴奋毒性作用。     

红藻氨酸诱导性癫痫发作大鼠海马cNOS及iNOS的变化及作用

目的研究组成型一氧化氮合酶（ｃＮＯＳ）及诱导型一氧化氮合酶（ｉＮＯＳ）在红藻氨酸（ＫＡ）诱导癫痫发作中的变化及作用。方法采用免疫组织化学方法显示ｃＮＯＳ及ｉＮＯＳ的变化;Ｎｉｓｓｌ染色显示神经元的损害。结果ＫＡ３０分钟ｃＮＯＳ较对照组明显增加（Ｐ＜０．０５）,随后下降至正常水平;ＫＡ诱导２小时ｉＮＯＳ明显升高,以ＣＡ１区为著,至ＫＡ６小时达高峰,然后在高水平缓慢下降;Ｎｉｓｓｌ染色神经元变性坏死ＣＡ３＝齿状回＞ＣＡ１。结论ＫＡ诱导癫痫发作导致海马ｃＮＯＳ及ｉＮＯＳ表达增多,神经元的坏死与ＮＯＳ表达增多无明显关系。     

尼莫地平辅助抗痫的临床研究

本文报告尼莫地平（Ｎｉｍｏｄｉｐｉｎｅ，ＮＭＤ）辅助抗病药（Ａｎｔｉｅｐｉｌｅｐｔｉｃ ｄｒｕｇｓ，ＡＥＤｓ）在抗病方面的临床价值。发现ＮＭＤ可使癫痫患者服用ＡＥＤｓ剂量减小而抑制癫痫发作效果保持或提高。特别是脑血管病后癫痫经小剂量ＡＥＤｓ加ＮＭＤ治疗后癫痫发作频度下降８９．６１％。ＮＭＤ可使某些ＡＥＤｓ血浓度提高。１０例在加用ＮＭＤ前后进行２９例外ＡＥＤｓ血浓度测定，加服ＮＭＤ后ＡＭＤｓ血浓度提     

脑缺血再灌流大鼠脑胶质源性神经营养因子基因表达的变化

探讨脑缺血再灌流不同时程及不同程度缺血对海马及皮层胶质源性神经营养因子（ｇｌｉａｌｃｅｌｌｌｉｎｅ ｄｅｒｉｖｅｄ ｎｅｕｒｏｔｒｏｐｈｉｃ ｆａｃｔｏｒ, ＧＤＮＦ）基因表达的影响,以及Ｎ甲基Ｄ天冬氨酸（Ｎｍ ｅｔｈｙｌＤｓａｐａｒｔａｔｅ, ＮＭＤＡ）受体拮抗剂,钙离子通道阻断剂是否能调节缺血病态下ＧＤＮＦｍ ＲＮＡ的表达。参照Ｓｍ ｉｔｈ 等方法建立大鼠前脑缺血再灌流动物模型。用ＤＩＧＯｌｉｇｏｎｕｃｌｅｏｔｉｄｅ ３′ｅｎｄ ｌａｂｅｌｉｎｇ Ｋｉｔ,标记５１ ｍ ｅｒ的ＧＤＮＦ寡核苷酸探针在含有海马结构的冰冻组织切片上进行原位杂交检测ＧＤＮＦｍ ＲＮＡ的表达。１０ ｍ ｉｎ 缺血再灌流２ ｈ,齿状回ＧＤＮＦｍ ＲＮＡ表达上调。再灌流６ ｈ,ＣＡ１,ＣＡ３ 和皮层ＰＡＲ区ＧＤＮＦｍ ＲＮＡ表达亦见增多,２４ ｈ 达高峰。Ｋｅｔａｍ ｉｎｅ 可使ＧＤＮＦ的基因表达在海马结构及皮层ＰＡＲ区明显低于相应的缺血再灌流组,统计学差异显著（Ｐ＜ ００５）。脑缺血再灌流时ＧＤＮＦ基因表达增加,对缺血神经元可能起保护作用。Ｋｅｔａｍ ｉｎｅ可阻断缺血后ＧＤＮＦｍ ＲＮＡ 的表达增加,提示ＮＭＤＡ谷氨酸受体很可能参与介导了缺     

单胺类递质在迷走神经刺激抗癫痫中的作用研究

目的探讨迷走神经刺激（ｖａｇｕｓｎｅｒｖｅｓｔｉｍｕｌａｔｉｏｎ,ＶＮＳ）抗癫痫的作用机制。方法成年健康Ｗｉｓｔａｒ大鼠３０只,随机分为正常对照组（ＮＣ组）、戊四氮（ｐｅｎｔｙｌｅｎｅｔｅｔｒａｚｏｌ,ＰＴＺ）致癫痫组（ＰＴＺ组）及ＶＮＳ后ＰＴＺ致癫痫组（ＶＮＳ组）。ＰＴＺ腹腔注射致癫痫后（６０ｍｇ／ｋｇ体重）,行左侧颈部迷走神经刺激。采用荧光光度法测定各组动物大脑顶叶皮层及海马的去甲肾上腺素（ＮＡ）、肾上腺素（Ａ）及五羟色胺（５ＨＴ）的含量。结果顶叶皮层Ａ及５ＨＴ的含量ＰＴＺ组明显高于ＮＣ组,而ＶＮＳ组则明显低于ＰＴＺ组;海马内ＮＡ、Ａ及５ＨＴ的含量ＰＴＺ组明显低于ＮＣ组,而ＶＮＳ组ＮＡ及５ＨＴ含量明显高于ＰＴＺ组。行为和ＥＥＧ结果显示,ＶＮＳ有明显的抗癫痫作用。结论单胺类递质ＮＡ、Ａ及５ＨＴ在ＶＮＳ抗癫痫中起重要作用。     

红藻氨酸诱导癫痫发作小鼠脑组织中NO^—2与硫代巴比妥酸反…

了解活性介质一氧化氮与癫痫发作的关系。用比色法检测红藻氨酸诱导ＢＡＬＢ／ｃ小鼠癫痫发作后，不同时点脑匀浆上清液中亚硝酸根与硫代巴比妥酸反应物的含量。ＮＯ＾－２浓度与ＴＢＡ反应物含量的多少与ＫＡ诱导的癫痫发作时程有关。在发作初期，ＮＯ＾－２随发作持续而增多，但发作后期又迅速减少。ＮＯ＾－２浓度的升高与减低受Ｌ－精氨酸及其硝基衍生物Ｎ＾Ｇ位硝基左型精氨酸的影响。     

GM1对大鼠全脑缺血再灌注中钙平衡紊乱,氧自由基代谢异常 …

目的 研究单唾液酸四己糖神经节苷脂（ＧＭ１）对大鼠全脑缺血再灌注中钙平衡紊乱、氧自由基代谢异常以及病理损伤的影响。方法 运用大鼠全脑缺血再灌注模型（４ＶＯ）,观察假手术组、脑缺血３０分钟再灌注６０分钟生理盐水（ＮＳ）处理组（ＮＳ组）和缺血３０分钟再灌注６０分钟ＧＭ１处理组（ＧＭ１组）的脑海马组织线粒体钙（ＭＣａ）、钙调素（ＣａＭ）、丙二醛（ＭＤＡ）及海马ＣＡ１区病理改变。结果 ＮＳ组海马组织ＭＣａ     

脑缺血对局部超氧化物岐化酶、丙二醛水平的影响

建立大鼠右大脑中动脉栓塞（ＲｉｇｈｔＭｉｄｄｌｅＣｅｒｅｂｒａｌＡｒｔｅｒｙＯｃｌｕｓｉｏｎＲ－ＭＣＡＯ）模型，检测局部缺血后不同时间左右脑组织超氧化物岐化酶（ＳｕｐｅｒｏｘｉｄｅＤｉｓｍｕｔａｓｅＳＯＤ）、丙二醛（ＭＤＡ）的含量，发现Ｒ－ＭＣＡＯ１０分钟始，缺血脑组织ＳＯＤ即降低，至３０分钟后恢复，而ＭＤＡ则在Ｒ－ＭＣＡＯ６０分钟后持续升高。说明缺血后ＳＯＤ活力下降、致ＭＤＡ蓄积，是造成脑组织损伤的机制之一。     

Prolonged neonatal seizures exacerbate hypoxic-ischemic brain damage: correlation with cerebral energy metabolism and excitatory amino acid release

BACKGROUND: Perinatal hypoxia-ischemia (HI) is the most common precipitant of seizures in the first 24-48 h of a newborn's life. In a previous study, our laboratory developed a model of prolonged, continuous electrographic seizures in 10-day-old rat pups using kainic acid (KA) as a proconvulsant. Groups of animals included those receiving only KA, or HI for 15 or 30 min, followed by KA infusion. Our results showed that prolonged electrographic seizures following 30 min of HI resulted in a marked exacerbation of brain damage. We have undertaken studies to determine alterations in hippocampal high-energy phosphate reserves and the extracellular release of hippocampal amino acids in an attempt to ascertain the underlying mechanisms responsible for the damage promoted by the combination of HI and KA seizures. METHODS: All studies were performed on 10-day-old rats. Five groups were identified: (1) group I--KA alone, (2) group II--15 min of HI plus KA, (3) group III--15 min of HI alone, (4) group IV--30 min of HI plus KA, and (5) group VI--30 min of HI alone. HI was induced by right common carotid artery ligation and exposure to 8% oxygen/balance nitrogen. Glycolytic intermediates and high-energy phosphates were measured. Prior to treatment, at the end of HI (both 15 and 30 min), prior to KA injection, and at 1 (onset of seizures), 3, 5 (end of seizures), 7, 24 and 48 h, blood samples were taken for glucose, lactate and beta-hydroxybutyrate. At the same time points, animals were sacrificed by decapitation and brains were rapidly frozen for subsequent dissection of the hippocampus and measurement of glucose, lactate, beta-hydroxybutyrate, adenosine triphosphate (ATP) and phosphocreatine (PCr). In separate groups of rats as defined above, microdialysis probes (CMA) were stereotactically implanted into the CA2-3 region of the ipsilateral hippocampus for measurement of extracellular amino acid release. Dialysate was collected prior to any treatment, at the end of HI (15 and 30 min), prior to KA injection, and at 1 (onset of seizures), 3, 5 (end of seizures), 7 and 9 h. Determination of glutamate, serine, glutamine, glycine, taurine, alanine, and GABA was accomplished using high-performance liquid chromatography with EC detection. RESULTS: Blood and hippocampal glucose concentrations in all groups receiving KA were significantly lower than control during seizures (p < 0.05). beta-Hydroxybutyrate values displayed the inverse, in that values were significantly higher (p < 0.01) in all KA groups compared with pretreatment controls during seizure activity. Values returned to control by 2 h following the cessation of seizures. Lactate concentrations in brain and blood mimicked those of beta-hydroxybutyrate. ATP values declined to 0.36 mmol/l in both the 15 and 30 min hypoxia groups compared with 1.85 mmol/l for controls (p < 0.01). During seizures, ATP and PCr values declined significantly below their homologous controls. Following seizures, ATP values only for those animals receiving KA plus HI for 30 min remained below their homologous controls for at least 24 h. Determination of amino acid release revealed elevations of glutamate, glycine, taurine, alanine and GABA above pretreatment control during HI, with a return to normal prior to KA injections. During seizures and for the 4 h of recovery monitored, only glutamate in the combined HI and KA group rose significantly above both the 15 min of HI plus KA and the KA alone group (p < 0.05). CONCLUSION: Under circumstances in which there is a protracted depletion of high-energy phosphate reserves, as occurs with a combination of HI- and KA-induced seizures, excess amounts of glutamate become toxic to the brain. The latter may account for the exacerbation of damage to the newborn hippocampus, and serve as a target for future therapeutic intervention.     

SD大鼠红藻氨酸诱导性癫痫发作时Nd活性的组织学观察

本研究根据形态学观察对一氧化氮（NO）在癫病发作中的意义进行探讨。方法：选用红藻氨酸（KA）诱导的复杂部分性癫痫模型。SD大鼠20只随机分为KA30、60、90、200min组及对照组。脑组织进行还原型辅酶II依赖性黄逸酶（NADPHd，Nd）染色。结果：①KA建模鼠全部出现点头、肢体抽搐、湿水样摇动、姿式失衡及全身强直一阵挛性惊厥；②在不同的脑区和同一脑区不同时点Nd阳性神经元的分布均不同；KA建模组Nd的表达比对照级低，在CA3区KA30min组Nd的表达比其它时点KA组低；在KA90min组大脑皮质Nd的表达与对照组相比无显著差异。结论：①Nd免疫阳性产物在不同的脑区分布不同。②一氧化氮合酶─—氧化氮（NOS－NO）途径可能参与癫痫的起动与传播，在癫痫发作的不同阶段，内源性NO的作用依赖于NO具体的氧化还原状态，且与其被释放的部位、时间、程度有关．在早期，NO起负反馈调节作用，即早期抗发作。     

The effect of electrical stimulation and lesioning of the anterior thalamic nucleus on kainic acid-induced focal cortical seizure status in rats

PURPOSE: The present study aimed to clarify the effect of electrical stimulation and lesioning of the anterior nucleus of the thalamus (ANT) on kainic acid (KA)-induced focal cortical seizures in a rat model. To address the mechanism underlying these anticonvulsant actions, cerebral glucose metabolism after ANT electrical stimulation and lesioning was also examined. METHODS: Wistar rats were divided into five major groups: control (n = 9), unilateral (n = 9), and bilateral (n = 9) ANT electrical stimulation, and unilateral (n = 9) and bilateral (n = 9) ANT lesioning. After KA injection, average clinical-seizure frequencies in each group were measured. Electrical stimulation of ANT was introduced after induction of seizure status epilepticus. Stimulation was on for 30 min and off for 30 min per 60-min cycle. Local cerebral glucose utilization (LCGU) was also measured by using [(14)C] 2-deoxyglucose autoradiography in three groups of rats: control (n = 7), bilateral ANT stimulation (n = 7), and bilateral ANT lesioning (n = 7). RESULTS: Unilateral ANT electrical stimulation and lesioning significantly reduced clinical seizure frequency, compared with control animals. Strikingly, no animals treated with bilateral ANT procedures demonstrated any clinical seizure. LCGU was markedly increased in the sensorimotor cortex, striatum, thalamus, mammillary body, and midbrain tegmentum of control group rats after KA injection, but no increase in LCGU was noted in rats treated with bilateral ANT lesioning or stimulation. CONCLUSIONS: The electrical stimulation and lesioning of ANT suppressed focal cortical clinical seizures induced by KA injection. Additionally, an analysis of cerebral metabolic changes indicated that these procedures might suppress the function as amplifier and synchronizer of seizure activity.     

Kainic acid seizures in the developing brain: status epilepticus and spontaneous recurrent seizures.

Acute and chronic effects of seizures induced by intraperitoneal (i.p.) injection of kainic acid (KA) were studied in developing rats (postnatal days (P) 5, 10, 20, 30, and adult 60). For 3 months following KA-induced status epilepticus, spontaneous recurrent seizure (SRS) occurrence was quantified using intermittent video monitoring. Latency to generalized seizures was then tested using flurothyl, and brains were histologically analyzed for CA3 lesions. In P5-10 rats, KA caused generalized tonic-clonic ('swimming') seizures. SRS did not develop, and there was no significant difference between control and KA-treated rats in latency to flurothyl-induced seizures. In contrast, rats P20 and older exhibited limbic automatisms followed by limbic motor seizures which secondarily generalized. Incidence and frequency of SRS increased with age. P20-30 rats with SRS had shorter latencies to flurothyl seizures than did KA-treated P20-30 rats without SRS or controls. KA-treated P60 rats (with or without SRS) had shorter latencies than controls to flurothyl seizure onset. SRS in P60 rats occurred sooner after KA than in P20-30 rats. CA3 lesions were seen in P20-60 rats with and without SRS, but not in P5-10 rats. These data suggest that there are developmental differences in both acute and chronic responses to KA, with immature animals relatively protected from the long-term deleterious effects of this convulsant.     

Limbic seizures without brain damage after injection of low doses of kainic acid into the amygdala of freely moving rats

Kainic acid (KA, 8-15 ng) was injected into the amygdala of conscious freely moving rats via chronically implanted fused silica cannulas. At 15-25 min after the injection, most rats suffered a limbic seizure attack of short duration, consisting of mastication, forelimb clonus, and raising on hind limbs, behaviorally indistinguishable from kindled seizures. Typically, the attack was followed by stereotypies, intense exploration, and by 1 or 2 more attacks. About 60 min after the injection, most rats appeared normal again and histopathological changes in their brains did not exceed those seen in vehicle-injected rats. In 3 cases, however, recurrent seizures culminated in behavioral status epilepticus 60-90 min after the injection. The status epilepticus was stopped by i.p. injection of diazepam (10 mg/kg) after a duration of 10 min (1 case) and 30 min (2 cases), respectively. After 10 min status epilepticus, we observed marginal neuronal damage with slight gliosis in both hippocampi (CA3 and CA1); after 30 min, hippocampal histopathology was more pronounced, with additional necrosis of the ipsilateral piriform cortex. After 0.8 microgram KA, a hundredfold higher dose, the incidence of limbic seizures during the first 40 min was not significantly higher (9/12) than after the lower KA doses (13/19). However, a significantly higher proportion of rats exhibited long-lasting seizure activity, associated with confluent destruction of CA3 pyramidal cells and additional seizure-related brain damage. Our results show that limbic motor seizures do not inevitably lead to histopathological changes in the brain, provided they do not culminate in a state of permanent seizure activity.     

The effect of octreotide on kainate-induced wet dog shakes and seizure activity in male and female rats

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity. There are sex differences in seizure susceptibility as well as in SS and NO activities in brain. The present study was undertaken to assess the effect of octreotide (OC), a stable SS analogue, on KA-induced WDS and seizures in rats, with emphasis on possible sex differences. WDS and seizures were induced by KA in male and female (proestrus) Sprague Dawley rats; OC or saline was injected 30 min before KA and the behavior was monitored for 120 min after KA. Octreotide increased the number of WDS and decreased the number of convulsions; this effect was more pronounced in males. Onset of KA-induced seizure activity was earlier in females than males; however, there was no effect of OC on seizure latency. Seizure activity started after the termination of WDS. These results show OC has opposite effects on WDS and convulsions, in that it stimulates the former and inhibits the latter. These results support our previous findings that WDS and seizure activity involve separate mechanisms and suggest that WDS may have an inhibitory effect on limbic seizures.     

THE EFFECT OF OCTREOTIDE ON KAINATE-INDUCED WET DOG SHAKES AND SEIZURE ACTIVITY IN MALE AND FEMALE RATS

Systemic kainic acid (KA) administration to rats triggers wet dog shakes (WDS) followed by epileptic seizures. Although WDS are often associated with the occurrence of seizures, we have recently shown that following nitric oxide (NO) synthesis inhibition, the number of WDS decreased; subsequently the onset of seizure activity was shortened, and the number of convulsions was increased. Somatostatin (SS), whose release appears to be controlled by NO, inhibits seizure activity. There are sex differences in seizure susceptibility as well as in SS and NO activities in brain. The present study was undertaken to assess the effect of octreotide (OC), a stable SS analogue, on KA-induced WDS and seizures in rats, with emphasis on possible sex differences. WDS and seizures were induced by KA in male and female (proestrus) Sprague Dawley rats; OC or saline was injected 30 min before KA and the behavior was monitored for 120 min after KA. Octreotide increased the number of WDS and decreased the number of convulsions; this effect was more pronounced in males. Onset of KA-induced seizure ac tivity was earlier in females than males; however, there was no effect of OC on seizure latency. Seizure activity started after the termination of WDS. These results show OC has opposite effects on WDS and convulsions, in that it stimulates the former and inhibits the latter. These results support our previous findings that WDS and seizure activity involve separate mechanisms and suggest that WDS may have an inhibitory effect on limbic seizures.     

Nonconvulsive Kainic Acid-Induced Seizures Elicit Age-Dependent Impairment of Memory for the Elevated Plus-Maze

The goal of this study was to evaluate changes in spatial learning in adult and immature rats during and after nonconvulsive seizures. An elevated plus-maze was used in 18- and 25-day-old and adult rats. Kainic acid (KA 6 mg/kg) was administered 60 minutes before the first exposure (Experiment 1) or after a 3-day pretraining (Experiment 2, only adult rats). Animals were retested three times with 24-hour intervals. EEG activity was monitored in 18-day-old rats. KA prolonged the transfer latency (TL) in all age groups. In the youngest group the TL was prolonged 24 hours after KA when epileptic EEG graphoelements were still registered. In both older groups, prolonged TL was measured only 60 minutes after KA. In the pretrained adults, significantly prolonged TLs persisted for 24 hours after KA. KA changed the performance of adult and immature rats in the elevated plus maze not only during nonconvulsive seizures but also 24 hours later.     

Effects of topiramate on seizure susceptibility in kainate-kindled rats: involvement of peripheral-type benzodiazepine receptors.

This study was aimed to quantitatively evaluate the effects of topiramate (TPM) on seizure susceptibility and hippocampal peripheral-type benzodiazepine receptors (PBRs) in the kainic acid (KA) model of temporal lobe epilepsy. Male rats were randomized into saline control group, KA group, KA/TPM low dose group and KA/TPM high dose group. Three weeks after single injection of KA (10 mg kg(-1), sc), the effects of TPM were tested at two doses (10 and 30 mg kg(-1), sc) once a day for 1 week in KA/TPM low dose group or KA/TPM high dose group, respectively. Rats in KA group received comparable injections of saline. Four weeks after initial KA injection, a subconvulsant dose KA (5 mg kg(-1), sc) was administered in rats in these three groups. Rats in saline control group received equal volume of saline. All animals were decapitated and hippocampus synaptosomes were purified 180 min after behavioral observation. PBRs specific binding sites were assessed by an in vitro binding technique utilizing the highly selective ligand [(3)H]PK11195. Seizure threshold was elevated and specific PBRs binding in hippocampus was decreased by TPM in dose-dependent manner. Specific PBRs binding in hippocampus was significantly related to seizure latency and seizure intensity. These results suggest that TPM can reduce the susceptibility to seizures in KA-kindled rats and its anticonvulsant effect seems resulting from, at least in part, the reduced PBRs binding after treatment. These results also support the hypothesis that PBRs represent a novel target for antiepileptic drug development.