快速点燃海马杏仁核建立癫癎鼠模型

目的：快速建立实验性癫癎动物模型。方法：１７ 只大鼠右侧海马和１１ 只鼠右侧杏仁核均埋植电极,用ＩＳ２ 型智能刺激器,以２００６００ μＡ 电脉冲刺激点燃海马杏仁核。结果：电刺激可诱发癎性发作和后放电,癎性行为分为五级,后放电呈高幅棘波。在点燃过程中,可记录到两种脑电活动：癎性脑电活动和自发性癎性脑电活动。随着电刺激次数的增多,发现Ⅱ、Ⅲ级癎性行为伴随较短的后放电时程,Ⅳ级以上癎性行为伴随较长的后放电时程。对原参数的刺激,大鼠癎性发作的敏感性增强并可持续数周。结论：应用低频短间隔电脉冲刺激大鼠海马或杏仁核可快速建立稳固的动物癫癎模型。     

点燃癫癎模型大鼠皮层与海马c-fos、c-jun基因的表达

目的:通过点燃癫癎模型大鼠脑内c-fos、c-jun基因表达的观察以探讨癫癎的发病机理.方法:选用大鼠杏仁核快速点燃癫癎模型,应用免疫组织化学技术观察点燃癫癎大鼠的皮层与海马c-fos、c-jun基因的表达.结果:杏仁核点燃癫癎大鼠的皮层与海马c-fos、c-jun基因表达明显增强,阳性细胞数量显著增加.结论:c-fos、c-jun基因的表达与癎性发作的机制相关.     

粉防己碱对戊四唑致(癎)大鼠皮层电图和海马超微结构的影响

目的:探讨钙拮抗剂粉防己碱(tetradrine,Tet)对戊四唑(Pentylentetrazol,PTZ)诱导的大鼠癫(癎)模型的作用.方法:健康SD大鼠24只,随机分为4组,对照组和Tet 3个剂量组(15 mg/kg,30 mg/kg,60 mg/kg)各6只.观察大鼠腹腔注射PTZ前后癫(癎)发作的情况,按Racine分级标准分级,同时记录皮层电图(ECoG),观察PTZ注射后到出现(癎)样放电的潜伏期及1 h内(癎)样放电累加的持续时间.电镜观察海马神经元超微结构的改变.结果:对照组给PTZ后均出现癫(癎)发作,程度均为5级,Tet组发作程度明显减轻.ECoG上出现(癎)样放电的潜伏期延长,(癎)样放电在1 h中的持续时间缩短.同时,Tet也能明显减轻PTZ致(癎)大鼠海马CA1区锥体细胞线粒体的损伤程度.结论:Tet对PTZ诱导的癫(癎)大鼠的发作有明显的对抗作用,对海马锥体神经元的拟伤具有保护作用.     

粉防己碱对戊四唑致大鼠皮层电图和海马超微结构的影响

目的:探讨钙拮抗剂粉防己碱(tetradrine,Tet)对戊四唑(Pentylentetrazol,PTZ)诱导的大鼠癫(癎)模型的作用.方法:健康SD大鼠24只,随机分为4组,对照组和Tet 3个剂量组(15 mg/kg,30 mg/kg,60 mg/kg)各6只.观察大鼠腹腔注射PTZ前后癫(癎)发作的情况,按Racine分级标准分级,同时记录皮层电图(ECoG),观察PTZ注射后到出现(癎)样放电的潜伏期及1 h内(癎)样放电累加的持续时间.电镜观察海马神经元超微结构的改变.结果:对照组给PTZ后均出现癫(癎)发作,程度均为5级,Tet组发作程度明显减轻.ECoG上出现(癎)样放电的潜伏期延长,(癎)样放电在1 h中的持续时间缩短.同时,Tet也能明显减轻PTZ致(癎)大鼠海马CA1区锥体细胞线粒体的损伤程度.结论:Tet对PTZ诱导的癫(癎)大鼠的发作有明显的对抗作用,对海马锥体神经元的拟伤具有保护作用.     

癫(癎)的生理性与病理性惊厥发作阈值的探讨

目的:探讨大鼠惊厥发作阈值由生理性向病理性过渡时的脑电变化,以及病理性惊厥发作阈值(癫癎发作阈值)与生理性惊厥发作阈值的区别.方法:以鼠模型作为观察对象,直接电刺激大鼠皮层测定惊厥阈值.连续11周给予大鼠皮层电刺激,每日两次,动态观察大鼠的惊厥发作时的刺激阈值、皮层脑电活动以及海马的病理改变情况.结果:实验最初大鼠皮层惊厥发作阈值高,局限性发作的惊厥阈值(TLS)为1 145±403.37μA,全面性发作的惊厥阈值(TGS)为1 277±443.15 μA,延续性发作的惊厥阈值(TPS)为1 449±472.45μA,但个体差异大,在电刺激开始的4周内,各组大鼠的惊厥发作阈值迅速下降.随着刺激时点延长其下降趋势逐渐平稳,至电刺激第10周逐渐稳定在一个较低的水平且不再变化,此时大鼠间个体差异亦减小(TLS 430±34μA),(TGS 480±46 μA),TPS 605±70μA),与刺激初期相比差异有显著意义(P＜0.01).强电流刺激组在第三周,弱电流刺激组在第八周分别出现了自发后放电现象,同期的海马组织学观察亦发现神经元缺失和损伤改变,对照组未见异常.结论:脑内存在的惊厥发作阈值应分为生理性和病理性两个阶段.而病理性惊厥发作阈值(癫癎发作阈值)是由病理因素造成的一种慢性脑损害结果,病理性的刺激因素与刺激强度对这一形成过程成正相关作用.     

丙戊酸和托吡酯治疗癫癎患者长程视频脑电图分析比较

目的:分析比较口服丙戊酸(Valproate,VPA)和托吡酯(Topiramate,TPM)对癫癎患者长程视频脑电图的影响。方法:对152例单独应用丙戊酸和129例单独应用托吡酯至少两年无发作的癫癎患者脑电图进行分析和比较,所有患者进行至少2次24小时长程视频脑电图检查,期间间隔至少2年。结果:结果:丙戊酸钠组,136例患者癫癎发作波明显减少或消失,15例患者癫癎发作波无明显减少,1例患者癫癎发作波增加;托吡酯组,112例患者癫癎发作波明显减少或消失,16例患者癫癎发作波无明显减少,1例患者癫癎发作波增加。两组比较,差异无统计学意义。结论 :丙戊酸钠和托吡酯均可使症状性癫癎或原发性癫癎的临床发作得到控制,与脑电图的改变基本一致。     

托吡酯转换治疗成人癫癎的研究

目的:评价托吡酯(妥泰)转换用药对成人癫癎的疗效和安全性.方法:对38例用卡马西平或丙戊酸钠治疗效果不佳的成人癫癎患者,加用托吡酯治疗,在加量时逐渐减少原来用药剂量,观察其有效性和安全性.结果:托吡酯转换治疗后,患者癫癎发作减少,其中无发作3例(7.9%),显效17例(44.7%),有效10例(26.3%),无效8例(21%),总有效30例(78.9%).结论:对用卡马西平或丙戊酸钠疗效不佳的患者转换用托吡酯是安全有效的治疗措施.     

托吡酯对癫癎患者脑电活动的影响

目的 :观察癫患者应用托吡酯单药治疗后 ,脑电背景活动及发作间歇期样放电的变化。方法 :对 42例癫患者给予托吡酯单药治疗 ,比较用药前和用药后 3个月时的脑电背景活动和发作间期样放电的变化及其与临床疗效的关系。结果 :用药 3个月时EEG的θ频段相对功率显著增加(P <0 0 5 ) ,α频段、δ频段、β频段相对功率改变不大 ;4例发作间期的样放电消失 ,6例明显减少 ,但样放电的改变与临床疗效无明显相关性 (P >0 0 5 )。结论 :托吡酯可使脑电背景活动中θ频段相对功率显著增加 ,发作间期的样放电减少 ,但样放电的改变与临床疗效无关     

青霉素致癎动物模型的电生理研究

目的:探讨青霉素致癫癎大鼠样发作的特点以及可能的电生理机制。方法:在立体定向指导下,将脑电图(EEG)记录电极植入24只Wistar大鼠海马、颞叶和额叶皮质中。手术后1周在大鼠清醒状态下,青霉素300万单位/kg(致组)或等容生理盐水(对照组)腹腔注射后连续描记EEG 120 min,观察大鼠行为表现及海马和大脑皮层EEG变化特点。结果:①青霉素致组大鼠样发作程度均达到Ⅳ-Ⅴ级;②同时在海马和皮层记录到各种形式的癎样放电波,如棘波、棘慢综合波、尖波、尖慢综合波、或阵发性节律等;③大多以同步放电起始,个别以海马或皮层先出现样放电,然后同步化。结论:①青霉素致惊厥大鼠的癎样发作基本上是全面性的,②其EEG主要是大脑皮质、海马同步放电开始。     

醒脑静对戊四氮致癎大鼠行为学及脑电图的影响

目的：探讨中成药醒脑静（XingNaoJing,XNJ）对戊四氮慢性点燃癫癎大鼠行为学及脑电图的影响。方法：将健康雄性SD大鼠50只随机分成5组（每组10只）：正常对照组、单纯模型组、制模并药物干预的醒脑静组、苯巴比妥组及中西药合用（醒脑静＋苯巴比妥）组,观察分析醒脑静对戊四氮点燃癫癎大鼠首次出现发作时间、各阶段发作级别、发作潜伏期及持续时间和脑电图的影响。结果：醒脑静组首次出现癫癎发作时间较模型组延迟（P〈0．01）,发作级别降低（P〈0．05,P（0．01）,发作潜伏期明显延长（P（0．01）,发作持续时间明显缩短（P〈0．01）,癫癎发作波频率和波幅降低。醒脑静组与苯巴比妥组比较,差异无统计学意义（P〉0．05）。中西药合用组各指标与醒脑静单用组或苯巴比妥单用组比较差异均有统计学意义（P（0．05）。结论：醒脑静具有抑制戊四氮诱发癫癎的作用,与抗癫癎西药合用抗癫癎作用更强。     

Effect of different patterns of low-frequency stimulation on piriform cortex kindled seizures

Low-frequency stimulation (LFS) is an antiepileptic and antiepileptogenic electrical stimulation. In this study the effect of changes in some LFS (1Hz, monophasic square wave) parameters (intensity, pulse duration and train duration) on piriform cortex kindled seizures was investigated both in fully kindled rats and during kindling acquisition. In fully kindled animals, application of different patterns of LFS immediately before kindling stimulation had no significant effect on seizure parameters. However, daily (15 min) application of LFS (0.1 ms pulse duration at intensity equal to after-discharge threshold (ADT) and 1 ms pulse duration at intensity equal to 1/4 ADT) during inter-seizure interval of 7 days significantly reduced the stage 5 duration of the next kindled seizure. Application of the same two LFS protocols for 3 days and 2 weeks had no effect on seizure parameters. The effect of LFS was also tested using different paradigms during kindling acquisition. When LFS (0.1 and 1 ms pulse duration, intensity equal to ADT and 1/4 ADT) was delivered daily after each kindling stimulation, it could significantly decrease after-discharge duration in various days during kindling development. In this experiment, only LFS with 0.1 ms pulse duration and intensity equal to ADT significantly delayed the appearance of seizure stages 1 and 2. According to obtained results, it may be concluded that in fully kindled rats application of different patterns of LFS before kindling stimulation has no anticonvulsant effect, but it can exert an inhibitory effect when applied during an inter-seizure interval of 7 days. In addition, LFS has antiepileptogenic effect during kindling acquisition. These effects depend on the applied LFS parameters (e.g. intensity, pulse duration and train duration).     

Edaravone,a free radical scavenger,retards the development of amygdala kindling in rats

This study evaluated the antiepileptogenic effects of edaravone, a newly developed radical scavenger, on the amygdala kindling rats. The afterdischarge duration (ADD), AD threshold (ADT), and seizure severity in animals were measured to study the anticonvulsant effects of edaravone (2 mg/kg or 20 mg/kg i.p. for 7 days) on fully kindled seizures. Furthermore, for the study of antiepileptogenesis effects of the drug (2 mg/kg or 20 mg/kg i.p. for 7 days), not only ADD and seizure severity during kindling but also both the pre- and post-kindling ADT were measured. Edaravone neither induces nor inhibits fully kindled seizures regardless of the dose; however high-dose edaravone (20 mg/kg) retarded kindling development together with shortened ADD and elevated ADT. The present data suggest that high-dose edaravone has an antiepileptogenic drug effect for the prevention of epilepsy. However, other chronic models and clinical trials are needed to confirm the effects of edaravone on the prevention of human epilepsy.     

杏仁基底外侧核电点燃癫痫模型的制作及观察

为了探讨杏仁基底外侧核电点燃癫痫模型的制作及意义,我们把双极电极插入大鼠左侧杏仁基底外侧核,给予慢性电刺激使大鼠达到点燃状态,观察其发作过程、行为改变并记录脑电图。结果发现29只接受刺激的大鼠,达到点燃的有24只,8.29±5.31次刺激出现5级瘸样发作,10.87±3.44次刺激达到点燃,没有因抽搐发作而致死的点燃大鼠。脑电图记录到后发放时程在32.05~51.65 s之间。行为观察发现点燃大鼠比对照组易激惹。说明杏仁基底外侧核电点燃大鼠癫痫模型便于从行为、脑电图等多方面进行观察,是研究人类癫痫机制、药物治疗和预防的良好工具。     

Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of acute phenytoin

This study addressed some of the controversial issues surrounding the anticonvulsant effect of phenytoin, and the predictive validity of the guinea-pig kindling model for the screening of anticonvulsant drugs. Following an intraperitoneal injection of either 50 or 75 mg/kg phenytoin, we analysed plasma concentrations of phenytoin at various time intervals. Behavioural toxicity was assessed at 0.5 h postinjection using quantitative locomotor tests, as well as scores on a sedation/muscle relaxation rating index. The anticonvulsant efficacy of phenytoin was evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD) and behavioural seizure severity at three phases of kindling: non-kindled, kindling acquisition (early and late) and kindled (50+ ADs). ADD and seizure severity were also measured in response to both threshold and suprathreshold kindling stimulation. Plasma levels of phenytoin corresponded to the human therapeutic range at the time of behavioural testing and kindling. Phenytoin did not exert significant adverse effects in guinea-pigs on both the behavioural tests and rating index. Phenytoin increased ADT in non-kindled and kindled guinea-pigs and effectively reduced ADD and seizure severity, indicating that the guinea-pig model correctly predicted phenytoin's anticonvulsant effect. Phenytoin produced reliable anticonvulsant activity in the guinea-pig at threshold stimulation but a somewhat reduced efficacy on seizure severity at suprathreshold stimulation intensities. Kindling in the guinea-pig is a valid model of human partial seizures.     

Conventional anticonvulsant drugs in the guinea-pig kindling model of partial seizures: effects of acute carbamazepine

This study addressed the anticonvulsant effect of carbamazepine (CBZ) in the guinea-pig kindling model to further test this model for the screening of anticonvulsant drugs. We analysed plasma concentrations of CBZ at various time intervals after intraperitoneal injection of either 10, 25 or 40 mg/kg CBZ. Behavioural toxicity was assessed at 0.5 h postinjection using quantitative locomotor tests, as well as scores on a sedation/muscle relaxation rating index. The anticonvulsant efficacy of CBZ was evaluated from measurements of afterdischarge threshold (ADT), afterdischarge duration (ADD), and behavioural seizure severity at three phases of kindling: non-kindled, kindling acquisition (early and late) and kindled (50+ ADs). ADD and seizure severity were also measured in response to both threshold and suprathreshold kindling stimulation. Plasma levels of CBZ were within, or higher, than the human therapeutic range at the time of behavioural testing and kindling. CBZ exerted slight effects in guinea-pigs on the sedation rating index but not the behavioural tests. CBZ increased ADT and reduced ADD and seizure severity throughout all phases of kindling, indicating that the guinea-pig model correctly predicts CBZ's anticonvulsant effect. CBZ in the guinea-pig kindling model produced consistent anticonvulsant activity that did not appear to be dependent on stimulation intensity.     

Fructose-1,6-diphosphate inhibits seizure acquisition in fast hippocampal kindling

Inhibition of glycolytic metabolism may provide a new therapy for refractory epilepsy. Fructose-1,6-diphosphate (FDP), which inhibits glycolysis and diverts glucose into the pentose phosphate pathway, has strong inhibitory action on seizures induced by chemical convulsants. Here, we investigated the effect of FDP on a rat model of rapid hippocampal kindling. After determining the after-discharge threshold (ADT), the seizure severity and after-discharge duration (ADD) were measured to study the antiepileptogenic effects of FDP (0.5 or 1.0 g/kg i.p. for 4 days). The mRNA expression levels of the brain-derived neurotrophic factor (BDNF) and its principal receptor TrkB, which are key modulators of seizure activity, were determined in the ipsilateral hippocampus by real-time polymerase chain reaction (RT-PCR). High-dose FDP (1.0 g/kg) delayed kindling development together with shortened ADD, and high-dose treated rats also needed more kindling stimulations and more cumulative ADD to stage 4. However, it showed no significant antiepileptogenic effect at a lower dose of 0.5 g/kg. In addition, FDP attenuated BDNF and TrkB expression before and during kindling procedure; this result indicated that BDNF/TrkB signaling pathway may participate in the antiepileptogenic action of FDP. Our data demonstrates that FDP has a significant antiepileptogenic effect in kindling seizures and that it may be a potential antiepileptic drug in the future.     

Amygdala kindling and muricide in rats

It was demonstrated that home cage muricide in the Wistar rat was uneffected by bilateral amygdala after-discharge threshold (ADT) reduction. The subsequent kindling of the amygdala, however, resulted in an apparent facilitation in the onset of the predatory response. In a larger predatory arena, the above manipulations had no effect upon the muricide response of Royal Victoria Hooded rats. There were no obvious amygdala EEG correlates of muricidal versus non-muricidal rats, e.g., differences in ADT, AD duration, kindling rate, etc. In addition, the ADT of the two amygdalae were seemingly independent. Similarly, ADT reduction and/or kindling had no effect upon the contralateral amygdala ADT. As has been previously shown, kindling of one amygdala significantly facilitated the rate of motor seizure development from the second, as well as provoking changes in the onset latency to motor seizure. The muricide data were discussed in the context of kindled induced synaptic facilitation and functional lesion effects.     

High frequency tendon reflexes in the human soleus muscle

The antiepileptic activity of hydrophilic extract of Vitex agnus castus fruit (Vitex) was evaluated by the kindling model of epilepsy. Intact male rats (250-300 g) were stereotaxically implanted with a tripolar and two monopolar electrodes in amygdala and dura, respectively. The afterdischarge (AD) threshold was determined in each animal and stimulated daily until fully kindled. The animals were administered different doses (60, 120 or 180 mg/kg) of Vitex or 0.1 ml of hydro alcoholic solvent intra-peritoneally (i.p.) and kindling parameters including AD threshold, seizure stages (SS), afterdischarge duration (ADD), stage 4 latency (S4L) and stage 5 duration (S5D) were recorded 30 min post-injection. The obtained data showed that even low dose (60 mg/kg) of Vitex could significantly increase the AD threshold and decrease the ADD and S5D (P<0.05). These changes were more significant with higher doses (120 or 180 mg/kg) for ADD (P<0.01) and S5D (P<0.001). Vitex at the dose of 120 mg/kg, induced significant increment in S4L (P<0.05). This effect was more prominent at the dose of 180 mg/kg (P<0.001). The latter dose could significantly reduce seizure stage (P<0.01) and most of the animals did not show S5. These results indicate that Vitex can reduce or prevent epileptic activity as demonstrated by reduction of ADD and S5D (length of convulsion) in a dose dependent manner. In conclusion, Vitex at appropriate dose can probably reduce or control epileptic activities.     

大鼠杏仁复合体向听皮层的神经投射

目的：研究大鼠杏仁复合体一听皮层的纤维投射。方法：HRP神经追踪方法结合微电泳技术，以及核黄逆行荧光标记技术。结果：HRP注射到听皮层，同侧杏仁外侧核、杏仁基底核、杏仁前区和杏仁前皮层观察到逆行标记细胞；HRP注射到杏仁外侧核和杏仁基底核，在同侧听皮层出现顺行标记纤维；核黄注入到听皮层，在同侧杏仁外侧核和杏仁基底核发现逆行标记细胞。结论：大鼠听皮层接受同侧杏仁复合体的神经投射。     

抗癫痫药妥泰对大鼠胚胎骨骼发育影响的研究

目的 研究妥泰(TPM)高、低剂量单药及与丙戊酸钠(VPA)合用对大鼠胚胎骨骼发育的影响。方法 采用妊娠雌性SD大鼠随机分为5组。实验组3组，于妊娠6～15d分别经口灌胃给予TPM40mg/kg，TPM80mg/kg和TPM40mg／kg VPA300mg／kg。阴性对照组同期经口灌胃给以等量的蒸馏水。阳性对照组于妊娠第11d一次性腹腔注射环磷酰胺(CP)10mg／kg于妊娠第20d处死孕鼠，将胎仔茜素红和阿利新蓝骨骼双染后，检查全身骨骼发育程度。结果 TPM高剂量组及与丙戊酸钠联合用组仔鼠骨骼发育迟缓，与阴性对照组相比有明显的差异。但TPM低剂量组无显著差异。结论 TPM在低剂量时对大鼠胚胎骨骼发育影响较小，而高剂量及与丙戊酸钠联合用药时影响较大。