氟桂利嗪对青霉素致痈效应和海马神经元单位放电的影响

目的：探讨Ca^2＋拮抗剂氟桂利嗪对青霉素致效应和海马神经元单位放电的影响.方法：Wistar大鼠随机分成3组.正常对照组;癫癎模型组：用青霉素钠按6 000 000 U·kg^-1腹腔注射;癫癎预处理组：造模前用盐酸氟桂利嗪 20 mg·kg^-1每隔12 h灌胃,共2次,于第2次给药2 h后制作模型.观察癫癎发作并记录海马神经元单位放电.结果： ①正常对照组大鼠共记录到24个单位海马神经元放电;②癫癎模型组共记录到78个单位海马神经元放电,癫癎发作程度强,发作频率高;③癫癎预处理组共记录到47个单位海马神经元放电,癫癎发作程度减轻,发作频率减少.结论：氟桂利嗪可抑制青霉素致效应,减少海马神经元的单位放电.     

依达拉奉对癫(癎)大鼠海马肿瘤坏死因子-α和白介素-1β表达的影响

目的 探讨依达拉奉对癫(癎)大鼠海马肿瘤坏死因子(TNF)-α和白介素(IL)-1β表达的影响.方法 36只Wistar大鼠随机分为依达拉奉组、癫(癎)组和正常对照组.应用戊四氮腹腔注射制作癫(癎)模型.依达拉奉组在造模前0.5 h及造模后立即、造模后12 h分别予以腹腔注射依达拉奉3 mg/kg.癫(癎)大鼠于造模后进行行为学观察.应用酶联免疫吸附(ELISA)法检测各组大鼠海马TNF-α和IL-1β的表达.结果 造模后,癫(癎)组12只大鼠均为Ⅴ级发作;依达拉奉组3只大鼠为Ⅴ级发作,2只为Ⅳ级发作,5只为Ⅲ级发作,2只为Ⅱ级发作.与正常对照组比较,依达拉奉组与癫(癎)组大鼠海马TNF-α、IL-1β的表达水平均明显增高(P<0.05～0.01);与癫(癎)组比较,依达拉奉组大鼠海马TNF-α、IL-1β的表达水平均明显降低(均P<0.01).结论 依达拉奉能明显降低癫(癎)大鼠海马TNF-α和IL-1β的表达水平,从而发挥抗癫(癎)作用.     

戊四氮点燃癫癎大鼠海马5-羟色胺能神经递质的动态研究

目的：观察戊四氮（PTZ）点燃癫癎形成过程中大鼠海马5-羟色胺（5-HT）能神经递质的变化。方法：用PTZ制作癫癎大鼠模型,将造模成功大鼠分为戊四氮急性发作组（PTZ 1组）和戊四氮慢性点燃组（PTZ 2组）,同时设立对照组（腹腔注射生理盐水）。在体微透析取样,观察大鼠行为、脑电图（EEG）和海马5-HT能神经递质的变化。结果：PTZ 1组癫癎发作时EEG自发放电逐级加重;癫癎发作时海马5-HT水平与对照组、发作前和发作后比较显著升高（P〈0.05）;海马5-羟吲哚乙酸（5-HIAA）水平差异无统计学意义;5-HT转化率（5-HIAA/5-HT）降低,差异有统计学意义（P〈0.05）。PTZ 2组点燃后大鼠出现自发癫癎发作,EEG在发作间期出现自发放电;5-HT和5-HIAA水平在点燃期、维持点燃期、对照组间比较差异有统计学意义（P〈0.05）。结论：大鼠癫癎发作时海马5-HT水平显著升高,发作后恢复正常;在癫癎形成过程中,早期5-HT水平一过性升高、PTZ点燃后和发作间期海马5-HT水平逐渐降低。     

核因子-κB活性抑制剂对癫(癎)大鼠的脑保护作用

目的 研究核因子-κB(NF-κB)活性抑制剂吡咯烷二硫代氨基甲酸盐(PDTC)对癫(癎)大鼠的脑保护作用.方法 将36只雄性SD大鼠随机分为癫(癎)组(14只)、PDTC干预组(PDTC组,14只)和假手术组(8只).采用海马注射海人酸(KA)方法制作癫(癎)大鼠模型,PDTC组大鼠造模前30 min给于腹腔注射PDTC150 mg,/kg;观察各组大鼠癫(癎)发作的潜伏期和初次至第6次≥Ⅳ级发作的时间(发作严重程度).应用HE染色和免疫组织化学染色,观察各组大鼠海马CA3区残存神经元数和NF-κB的表达.结果 PDTC组大鼠癫(癎)发作潜伏期[(89.6±39.3)min]长于癫(癎)组[(67.5±22.9)min],但差异无统计学意义;PDTC组初次至第6次≥Ⅳ级发作的时间[(29.2±20.4)min]较癫(癎)组[(12.1±4.0)min]显著延长(P＜0.05);与癫(癎)组相比,PDTC组大鼠海马CA3区残存神经元数显著增多(P＜0.05),NF-κB表达水平显著降低(P＜0.01),二者间呈负相关(r=-0.562,P=0.001).结论 NF-κB活性抑制剂能降低癫(癎)发作严重程度,减少海马神经元的变性死亡,具有脑保护作用.提示癫(癎)发作所致脑组织损伤可能与NF-κB活化有关.     

胞二磷胆碱、氯脂醒、神经节苷脂对大鼠癫(癎)的影响

目的 探讨胞二磷胆碱、氯脂醒、神经节苷脂(GM1)对青霉素致(癎)大鼠行为学及脑皮层电图的影响,为临床治疗颅脑损伤和外伤后癫(癎)提供理论依据.方法 制作大鼠癫(癎)模型,观察并比较对照组、模型组、胞二磷胆碱组、氯脂醒组、GM1组大鼠的行为学及脑皮层电图表现.结果 胞二磷胆碱、氯脂醒、GM1均不能阻止青霉素诱导的大鼠癫(癎)发作.胞二磷胆碱、GM1可以延长青霉素诱导的大鼠癫(癎)(癎)波潜伏期、阵挛强直波潜伏期,减少阵挛强直总时间.结论 胞二磷胆碱、氯脂醒、GM1均不能阻止青霉素诱导的大鼠癫(癎)发作;胞二磷胆碱、GM1可以延长青霉素诱导的大鼠癫(癎)(癎)波潜伏期、阵挛强直波潜伏期,减少青霉素腹腔注射后50 min内的阵挛强直总时间.     

氟桂利嗪对癫痫鼠痫性发作和脑电活动的影响

目的研究氟桂利嗪对青霉素致癎大鼠癎性发作和脑电活动的影响.方法用60只Wistar大鼠分4组,即对照组及氟桂利嗪10、20、40 mg·kg-1组,2 h后对照组和各实验组给同样剂量青毒素300 万U·kg-1腹腔注射,观察大鼠行为表现及EEG改变.结果氟桂利嗪能明显降低青霉素致癎大鼠癎性发作程度,明显缩短癎性发作持续时间,显著延长癎性发作的潜伏期,明显提高存活率;明显延长大脑皮质、海马癎性放电潜伏期,缩短其持续时间,明显减少癎性放电的数量.结论氟桂利嗪对青霉素致癎大鼠的癎性行为和大脑皮质、海马的癎性电活动均有抑制作用.     

雌激素和克罗米酚对致癎大鼠海马γ-氨基丁酸免疫反应细胞和GABA_A受体α1亚单位表达的影响

目的了解雌激素和克罗米酚对海人藻酸(KA)致癎大鼠癫癎发作行为学的影响及其影响癫癎活动的部分机制。方法将去势的雌性大鼠添加雌激素(20mg/kg)或添加雌激素和克罗米酚治疗,比较各组大鼠致癎后癫癎发作的行为学变化;并采用间接免疫荧光法检测各组大鼠海马中γ-氨基丁酸(GABA)免疫反应细胞及GABAA受体α1亚单位表达的变化。结果添加雌激素治疗组大鼠癫癎发作的潜伏期和到达4/5级(4级或5级)的时间[分别为(24.63±11.44)min和(41.50±16.22)min]均较去势组[分别为(46.75±14.61)min和(65.13±12.99)min]明显缩短,而同时添加雌激素和克罗米酚治疗组的潜伏期[(43.50±5.75)min]比单纯添加雌激素组明显延长。雌激素组的阳性免疫反应细胞数在大鼠海马的某些区域也较去势组明显减少,克罗米酚组与雌激素组相比则有所增多。结论高水平的雌激素可促进癫癎发作,克罗米酚添加治疗具有一定的抗癫癎作用。这可能与脑内GABA能系统某些功能的改变有关。     

生酮饮食对海人酸点燃癫癎模型大鼠海马神经元保护作用研究

目的探讨生酮饮食对海人酸点燃癫癎模型大鼠海马神经元的保护作用。方法经海人酸制备SD大鼠癫癎模型,分别给予生理盐水+正常膳食(C组)、生理盐水+生酮饮食(K组)、海人酸+正常膳食(E组)和海人酸+生酮饮食(EK组),连续观察21 d后记录不同处理组大鼠体重、观察Ⅳ或Ⅴ级癫癎发作频率和持续时间,并通过HE染色和Nissl染色计数E组和EK组大鼠海马CA3区正常锥体神经元数目。结果 C组和K组大鼠均无癫癎发作,且海马CA3区锥体神经元数目正常。E组和EK组大鼠在观察过程中均出现Ⅳ或Ⅴ级癫癎发作,但EK组大鼠在饲养第21天时与E组相比,癫癎发作频率减少[(17.90±4.12)次对(30.50±4.40)次,P=0.000]、发作持续时间缩短[(212.70±17.75)s对(335.00±14.21)s,P=0.000],差异有统计学意义;EK组海马CA3区正常锥体神经元数目与E组相比增加[(117.67±7.51)个对(71.33±6.11)个,P=0.000],差异亦有统计学意义。结论生酮饮食对海人酸点燃癫癎模型大鼠海马神经元具有保护作用。     

海藻氨酸致癫癎状态大鼠海马区神经元损伤与Mg2+作用的研究

目的观察海藻氨酸(KA)诱导的癫癎状态(SE)大鼠海马神经元的形态学改变和Mg2+的神经保护作用.方法选用成年雄性Wistar大鼠75只,随机分为KA组、Mg2+组和生理盐水对照组.用KA诱导大鼠SE 3 h,Mg2+组大鼠在注射KA前腹腔内注射硫酸镁100 mg/kg,在癫癎发作终止后72 h将动物处死,分别用光镜和电镜观察海马神经元形态学改变.结果 KA组大鼠注射KA后(16.1±4.7)min出现癫癎发作,Mg2+组大鼠为(25.4±6.2)min,两组比较差异有显著性(P<0.05).KA组和Mg2+组大鼠在海马区均出现了嗜酸性神经元,Mg2+组大鼠神经元损伤程度明显低于KA组.结论 KA诱导的SE可导致海马神经元坏死,而 Mg2+作为兴奋性氨基酸拮抗剂对海马神经元具有保护作用.     

丙戊酸钠对戊四氮致癎大鼠海马Bax和Bcl-2表达的影响

目的探讨丙戊酸钠(VAP)对戊四氮(PTZ)致癎大鼠海马Bax和Bcl-2表达的影响.方法将24只成年Wistar大鼠随机分为正常对照(NC)组、PTZ组和VAP组,PTZ组和VAP组大鼠腹腔注射阈下剂量的PTZ 35 mg/(kg·d),直至达到点燃标准.点燃后,VAP组大鼠经腹腔注入VAP 15 mg/(kg·d),PTZ组大鼠经腹腔注入生理盐水,30 min后,再腹腔注射PTZ诱发癫癎发作.应用免疫组化法检测大鼠海马神经元Bax和Bcl-2蛋白的表达.结果大鼠海马神经元Bax阳性细胞数和光密度,PTZ组均明显高于VAP组和NC组(均P<0.01),VAP组明显高于NC组(P<0.05);大鼠海马神经元Bcl-2阳性细胞数和光密度,PTZ组明显高于NC组(P<0.05),VAP组均明显高于PTZ组和NC组(均P<0.01).结论 VAP可以增强癫癎大鼠海马神经元Bcl-2的表达和降低Bax的表达,有对抗癫癎发作导致细胞凋亡的作用.     

Anticonvulsive effects of quinine on penicillin-induced epileptiform activity: an in vivo study.

Epilepsy is an important problem in neurological disorders. The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. Recent studies claimed that gap junctions have a critical role in epileptic neuronal events. The aim of present study is to investigate the effects of connexin36 (Cx36) channel blocker quinine on penicillin-induced experimental epilepsy. For this purpose, 4 months old male Wistar rats were used in the present study. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. At the end of the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When the epileptiform activity, monitored from a digital recording system, reached maximal frequency and amplitude, quinine (200, 400 or 1000 nmol) was administered similar to penicillin. Effects of quinine on epileptiform activity were assessed by both electrophysiological and behavioral analysis. Quinine suppressed epileptiform activity by decreasing the amplitude and frequency of epileptiform spikes and by attenuating the epileptiform behavior. The outcomes of this study suggest that the blockade of Cx36 channels may contribute to the amelioration of epileptic activity.     

托吡酯对多巴胺能神经元保护作用研究

目的研究托吡酯对帕金森病大鼠多巴胺能神经元的保护作用。方法将48只雄性Sprague-Dawley大鼠随机分成4组:生理盐水组(A组),6-OHDA组(B组),造模前托吡酯预处理组(C组)和造模后托吡酯处理组(D组),每组各12只;第1～3dA、B、D组分别行生理盐水灌胃,C组用托吡酯稀释后灌胃;第4dB、C、D组分别向右侧纹状体注入6-OHDA,A组注入生理盐水;第5～7dA、B、C组行生理盐水灌胃,D组用托吡酯(剂量同前)稀释后灌胃;分别于造模后第4、28d断头处死,用免疫组织化学方法观察黑质区域内酪氨酸羟化酶(TH)阳性细胞数量,用分光光度计测定纹状体内超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-PX)和丙二醛(MDA)含量。结果与B组损毁侧比较,C、D组损毁侧黑质TH阳性细胞计数明显增多(P<0.01),纹状体内SOD及GSH-Px活性显著增高,MDA含量明显降低,同时C、D组比较差异有显著性(P<0.01)。结论托吡酯对多巴胺能神经元具有保护作用,其保护机制可能与降低脂质过氧化水平及毒性产物的作用和减少自由基的产生有关。     

Taurine- and penicillin-induced epileptic activity

The present study has been performed to investigate the effect of i.v. administration of taurine on the electrical activity of the epileptogenic focus induced by penicillin applied to the right sensory motor cortex of adult rats. Taurine (100 mg/kg body weight) was administered 15, 30, 60, and 120 min before the application of penicillin. The EEG was unipolarly recorded by means of electrodes applied to the pia. Taurine caused a decrease of the frequency as well as the spike amplitude of epileptic discharge. The spread of epileptogenic foci to the opposite hemisphere was retarded when compared to that of control animals. The maximal antiepileptic effect of taurine was observed when the amino acid was administered 30-60 min previous to penicillin. It is suggested that high concentrations of taurine in the brain might be necessary to inhibit the epileptic activity.     

The effects of octanol on penicillin induced epileptiform activity in rats: an in vivo study

The common features of all types of epilepsy are the synchronized and uncontrolled discharges of nerve cell assemblies. The reason for the pathologically synchronized discharges of the neuron is not exactly known yet. Recent reports claim that gap junctions have a critical role in neuronal synchronization. The present study was planned to investigate the effects of octanol, a gap junction blocker, on penicillin-induced experimental epilepsy. Permanent screw electrodes allowing EEG monitoring from conscious animals and permanent cannula providing the administration of the substances to the brain ventricle were placed into the cranium of rats under general anesthesia. After the postoperative recovery period, epileptiform activity was generated by injecting 300 IU crystallized penicillin through the ventricular cannula. When epileptiform activity, monitored from a digital recording system, reached at its maximum intensity, octanol was applied in the same way as penicillin administered. Application of octanol caused an inhibition in the epileptiform activity. Vehicle solution alone did not affect the epileptiform activity. Results of this study suggest that the blockade of electrical synapses may contribute to the prevention and amelioration of epileptic activity. Production of gap junction blockers selective for connexin types is needed. Further studies on the differential roles of gap junctions on certain epileptiform activities are required.     

Anticonvulsant effect of Annona diversifolia Saff. and palmitone on penicillin-induced convulsive activity. A behavioral and EEG study in rats

PURPOSE: To evaluate hypnotic and anticonvulsant activities of Annona diversifolia Saff. and palmitone by using behavior and electroencephalographic (EEG) analysis in an experimental model of focal seizures in rats. METHODS: For hypnotic assessment, EEG analysis of polysomnographic slow-wave sleep (SWS) and rapid eye movement (REM) sleep for a 1 h period were performed after vehicle, A. diversifolia extract or palmitone, administration. For anticonvulsant effect, 60 minutes after treatments, EEG and behavior were analyzed during penicillin-induced seizures. Latency to the onset of the first paroxystic spike, first seizure and frequency, as well as seizure severity using Racine's scale, were determined. RESULTS: Palmitone, but not A. diversifolia extract, produced a delay in the latency to the SWS phase. In addition, both palmitone and extract decreased SWS duration and accumulated REM sleep phase. With regard to the seizures, both the extract and palmitone increased the latency to the onset of spikes and seizures, but also decreased the duration of penicillin-induced seizures. This reduction in the EEG recordings was associated with an attenuation in the severity of behavioral seizures. CONCLUSIONS: A. diversifolia and palmitone did not produce a sedative-hypnotic effect although both of them were effective in reducing the severity of behavioral and EEG seizures induced by penicillin in rats, suggesting that the diminution in the paroxystic activity by A. diversifolia is likely produced by palmitone through GABAergic neurotransmission. This study justifies and reinforces the traditional use of this plant in epilepsy.     

Secondary generalization of seizures from a cortical penicillin focus following stimulation of the basal forebrain

The basal forebrain has been implicated in the regulation of generalized motor convulsive activity particularly from amygdala kindling. The effect of electrical stimulation of the substantia innominata and ventral pallidal regions of the basal forebrain in rats with acute interictal penicillin foci in the frontal parietal neocortex was determined. Stimulation of this area resulted in generalized cortical EEG synchronization, an inconsistent effect on interictal spike frequency, and generalized seizures that were not prevented by atropine. The results support a role for these basal forebrain structures in the regulation of generalized seizures from a cortical focus mediated primarily through influences on thalamocortical pathways.     

Antiepileptic and antiamnesic effect of carbamazepine in experimental limbic epilepsy.

Carbamazepine (20 mg/kg, 40 mg/kg or 60 mg/kg) given three times a day, has been demonstrated to have a significant anti-epileptic effect in rats with chronic limbic epilepsy induced by injecting tetanus toxin bilaterally into their hippocampi. This effect involved a reduction in the maximum number of fits occurring on one day, and with the highest dose, a significant reduction in the total number of fits. In a pilot experiment in which continuous EEG records were obtained throughout the syndrome, it appeared that the effect of carbamazepine was to reduce the proportion of EEG seizure discharges which lead to overt motor fits. With the higher drug dose plasma levels of carbamazepine were maintained around 2 micrograms/ml. This experimental epilepsy produces enduring deficits in the rats' memories for a light-discrimination task in a Y-maze learned before induction of epilepsy (8 weeks after initial learning). If the rats are dosed with carbamazepine during their epilepsy this memory deficit is abolished.     

痫性放电实现异体间转道并致痫动物的研究报道

目的观察青霉素癫痫模型痫性放电能否被引导电极转道至异体大鼠脑内并致痫。方法实验大鼠海马局部注射青霉素建立癫痫模型,通过引导电极拟将痫性放电导入异体大鼠同侧海马,观察实验大鼠的行为学、脑电图变化。结果致痫组、痫能导出组12只大鼠全部点燃,痫能导入组6只大鼠亦出现痫性发作,痫能导出组痫性发作时程缩短,致痫组、痫能导出组、痫能导入组大鼠脑电图均可记录到痫性波;对照组、电极组无痫性发作。结论实验性痫性放电可通过引导电极在异体大鼠脑组织间传导,脑内痫性放电有可能被电极导出。     

Suppression of Interictal Spikes and Seizures by Stimulation of the Vagus Nerve

The effects of electrical stimulation of the vagus nerve, a proposed treatment for patients with intractable epilepsy, on focal interictal spikes produced by penicillin and EEG secondarily generalized seizures induced by pentylenetetrazol were assessed in rats. Interictal spike frequency was reduced by 33% during 20 s of stimulation (p < 0.001) and remained low for ≤3 min. Amplitude of residual spikes was also decreased. Cardiac and respiratory rates were suppressed. Cooling the nerve proximal to the point of stimulation abolished the EEG and respiratory effects. A similar reduction in spike frequency of 39% was obtained by heating the animals' tail (p < 0.01). Vagal stimulation at onset of seizures reduced mean seizure duration from 30.2 ± 15.7 s without stimulation to 5.0 ± 1.8 s (p < 0.01). Only the EEG equivalent of the clonic phase of the seizure was affected. These findings suggest that vagus nerve stimulation can be a potent but nonspecific method to reduce cortical epileptiform activity, probably through an indirect effect mediated by the reticular activating system.     

青霉素与海人酸癫痫模型的比较

目的 通过用青霉素、海人酸2种药物制作癫痫模型,探讨2种致痫剂的作用特点及应用条件.方法 取健康雄性昆明小鼠90只,分为3组,对照组(n=10)、青霉素致痫组(n=40)和海人酸致痫组(n=40),青霉素致痫组腹腔注射青霉素7×106 U/kg,海人酸致痫组腹腔注射海人酸10mg/kg,生理盐水组腹腔注射生理盐水35 μL/g.注射后连续5 h观察小鼠是否有痫性发作并分级,进行脑电图描记.结果 空白对照组无痫性发作,两模型组均出现痫性发作,海人酸致痫组与青霉素致痫组按Racine分级0～Ⅴ级各级之间无明显差异(P＞0.05),小鼠出现癫痫的潜伏期海人酸致痫组比青霉素致痫组短(P<0.05),而且海人酸致痫组比青霉素致痫组死亡率低(P<0.05).结论 腹腔注射海人酸所致的动物模型具有与人类颞叶癫痫极为相似的癫痫发作行为学、脑电图特征,是理想的模拟人类颞叶癫痫的动物模型.