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.     

癫(癎)幼鼠海马和颞叶皮质区缝隙连接蛋白43和突触体素表达的变化

目的观察神经元缝隙连接蛋白43(Cx43)和突触体素(synaptophysin P38)在戊四氮(PTZ)点燃癫癎幼鼠海马及颞叶皮质区中的表达,探讨两者与癫癎的关系及其在癫形成中的作用。方法将50只21日龄Wistar大鼠分为对照组和实验组。实验组采用PTZ点燃癫癎幼鼠,按点燃进程分为Ⅰ级、Ⅱ级、Ⅲ级、Ⅳ级及Ⅴ级发作组。采用免疫组化和图像分析技术,观察海马及颞叶皮质区Cx43和P38表达的变化。结果应用PTZ点燃后,实验各组幼鼠海马及颞叶皮质区Cx43和P38的表达明显高于对照组(P<0.01),且随发作级别的增高,幼鼠海马及颞叶皮质各区Cx43和P38的表达均增加。但各组间海马区和颞叶皮质区Cx43和P38的表达情况的比较差异无统计学意义(P>0.05)。结论Cx43和P38的表达水平与癫癎的发生发展有密切关系,为研究小儿癫癎的病因及发病机制提供依据。     

立体定向方法建立大鼠红藻氨酸颞叶癫疒间模型及其脑电活动的实验研究

目的探讨采用立体定向技术建立大鼠颞叶癫癎模型的方法,并对发作后的脑电活动进行研究。方法用立体定向方法在20只SD大鼠的右侧海马注射红藻氨酸,用视频监测大鼠的行为学变化;在双侧海马、额叶皮质、杏仁核置入深部电极,对大鼠脑电活动进行长期记录。结果根据Racine行为学分级法,Ⅴ级6只,Ⅳ级10只,Ⅲ级3只,Ⅱ级1只;深部电极描记出起源于海马并向额叶皮质、杏仁核等传导癫疒间样波;病理变化提示长期癫疒间发作会导致海马锥体细胞逐渐缺失、坏死。结论用立体定向技术建立大鼠红藻氨酸颞叶癫疒间模型是一种可靠、经济和实用的方法。起源于海马并向额叶皮质、杏仁核等传导的癫疒间样波是颞叶癫疒间模型的神经电生理基础。     

戊四氮点燃猫癫痫形成过程中行为和脑电的动态研究

目的:观察戊四氮点燃猫癫癎形成过程中行为和脑电特征。方法:用低于急性致惊厥剂量的戊四氮(PIZ,25 mg·kg~1)给成年雄性猫每日肌肉注射,观察脑电活动和行为特征。结果:1周后,猫出现发作性面部抽搐,脑电为不对称近额部的散发性棘波,基本节律存在;2周后出现节律性点头,脑电为双侧对称性广泛的散发性棘慢波;16 d后出现发作性四肢强直,脑电活动背景节律变慢,棘慢波呈现阵发性;20 d后出现持续半小时以上的全面性强直阵挛发作,脑电活动为较多不规则的θ和δ波,棘慢波持续时间明显延长。结论:PTZ点燃猫癫癎形成过程中,其行为和脑电阶段性变化明显,与人类癫癎的局灶性继发全面性发作癫癎表现相似。     

胍丁胺对戊四氮诱导慢性癫癎大鼠的保护作用和海马星形胶质细胞表达的影响

目的:探讨不同剂量胍丁胺对戊四氮诱导的慢性癫癎大鼠模型的保护作用及对海马区星形胶质细胞表达的影响。方法:连续28 d腹腔注射戊四氮35 mg.kg-1建立大鼠慢性癫癎模型。不同剂量胍丁胺(20、40、80 mg.kg-1)进行干预。观察大鼠癫癎发作行为学及海马的形态学变化,检测海马星形胶质细胞的表达。结果:胍丁胺40、80 mg.kg-1可降低癫癎发作的日均等级评分,减少海马神经元丢失及星形胶质细胞增生。结论:胍丁胺40、80 mg.kg-1可抑制慢性癫癎大鼠发作,降低惊厥发作后海马星形胶质细胞的异常增生及神经元损伤。     

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。     

维拉帕米对耐苯妥英钠和卡马西平癫(癎)模型大鼠电生理和行为的影响

目的 观察P-糖蛋白(PGP)拮抗剂维拉帕米对耐苯妥英钠(PHT)和卡马西平(CBZ)癫(癎)大鼠电生理指标和行为学的影响.方法 建立慢性杏仁核点燃癫(癎)大鼠模型,筛选出耐药组和治疗有效组,给予维拉帕米,观察其对各组大鼠后放电阈值(after discharge threshold,ADT)、后放电时程(after discharge duration,ADD)等电生理指标和行为学的影响.结果 相对于耐药对照组,耐药组大鼠在预先给予维拉帕米后,使用抗癫(癎)药物后ADT[(238.0±32.2)μA]明显高于耐药对照组[(177.0±23.3)μA,P＜0.05];ADD时程明显缩短,Racine行为分级明显下降(P＜0.05).结论 维拉帕米可以协助抗癫(癎)药物(AEDs)改善耐药大鼠的电生理活动,降低点燃后发作分级,提示有效抑制PGP有助于改善多药转运体高表达导致的癫(癎)耐药.     

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。     

脑电刺激治疗难治性癫(癎)

脑电刺激治疗为不适合手术的难治性癫(癎)病人提供了一种选择,主要包括脑深部刺激、迷走神经刺激和闭合环路刺激.前两者主要通过调控丘脑-皮质通路来抑制皮质兴奋性,减少癫(癎)发作;后者通过早期预警触发刺激来抑制发作的传播扩散.本文就几种脑电刺激治疗的原理、方法、疗效和并发症等方面内容进行简要回顾总结.     

低频电刺激丘脑底核对癫(癎)大鼠海马谷氨酸和γ-氨基丁酸表达的影响

目的 探讨低频电刺激(LFS)丘脑底核对癫(癎)大鼠海马谷氨酸(Glu)及γ-氨基丁酸(GABA)表达的影响.方法 用30只大鼠制备杏仁核电刺激点燃模型,同时在丘脑底核埋置刺激电极;制模成功的大鼠随机分为LFS组及对照组;两组大鼠每日点燃1次,共10 d;LFS组大鼠每次点燃前予以LFS丘脑底核.观察10 d后两组大鼠癫(癎)发作程度和持续时间,应用免疫组化法测定大鼠海马Glu、GABA阳性细胞数及灰度值.结果 与对照组比较,LFS组癫(癎)发作的Racine评分明显降低,癫(癎)发作持续时间明显缩短;海马GABA阳性细胞数明显增多、灰度值降低;Glu阳性细胞数明显减少,灰度值明显增加(均P＜0.05＝.结论 LFS丘脑底核能有效抑制大鼠杏仁核点燃发作,其作用机制可能是改变了脑内Glu、GABA的表达.     

Right-sided vagus nerve stimulation reduces generalized seizure severity in rats as effectively as left-sided

As currently utilized, vagus nerve stimulation (VNS) is applied to the cervical trunk of the left vagus nerve to suppress seizures clinically. Demonstration that VNS can also reduce seizure severity when electrodes are placed on the right cervical vagus nerve in rats would provide empirical evidence that the antiepileptic effects of VNS are not an exclusive property of the left vagus nerve. Rats were implanted with a custom cuff electrode on either the left or right cervical vagus nerve. Two days later, continuous VNS was begun in half the rats with left-sided and half with right-sided electrodes. The remaining rats were connected to the stimulator, but did not receive VNS. After 30s, pentylenetetrazole (PTZ) was administered systemically and seizures were rated by a blinded observer. The PTZ test was repeated two days later, with VNS administered to the previously unstimulated rats, while the others received no stimulation. VNS significantly reduced the severity of PTZ-induced seizures in rats regardless of the side of stimulation as compared to their no-VNS (control condition) seizure severity. No significant differences in efficacy existed based on the side of stimulation. These results indicate that right-sided VNS in rats is just as effective as left-sided VNS, suggesting that fibers necessary for seizure suppression are not unique to the left vagus nerve.     

Modulation of seizure threshold by vagus nerve stimulation in an animal model for motor seizures

De Herdt V, De Waele J, Raedt R, Wyckhuys T, El Tahry R, Vonck K, Wadman W, Boon P. Modulation of seizure threshold by vagus nerve stimulation in an animal model for motor seizures.
Acta Neurol Scand: 2010: 121: 271–276.
© 2009 The Authors Journal compilation © 2009 Blackwell Munksgaard. Objective – The precise mechanism of action of vagus nerve stimulation (VNS) in suppressing epileptic seizures remains to be elucidated. This study investigates whether VNS modulates cortical excitability by determining the threshold for provoking focal motor seizures by cortical electrical stimulation before and after VNS. Material and methods – Male Wistar rats (n = 8) were implanted with a cuff‐electrode around the left vagus nerve and with stimulation electrodes placed bilaterally on the rat motor cortex. Motor seizure threshold (MST) was assessed for each rat before and immediately after 1 h of VNS with standard stimulation parameters, during two to three sessions on different days. Results – An overall significant increase of the MST was observed following 1 h of VNS compared to the baseline value (1420 μA and 1072 μA, respectively; P < 0.01). The effect was reproducible over time with an increase in MST in each experimental session. Conclusions – VNS significantly increases the MST in a cortical stimulation model for motor seizures. These data indicate that VNS is capable of modulating cortical excitability.     

迷走神经刺激术治疗顽固性癫痫初步探讨

目的 探讨迷走神经刺激术治疗顽固性癫痫的治疗效果.方法 对21例顽固性癫痫患者进行迷走神经刺激手术治疗,术后2周开机,分次调试参数,脉冲发生器输出电流从0.25 mA逐渐增加,但不超过3.0 mA,刺激时间为30 s,间歇5 min,信号频率为20～30 Hz,脉宽为250～1000μs.对治疗效果进行随访,分析治疗效果.结果 经4-16个月刺激,McHugh Ⅰ级3例,Ⅱ级7例,Ⅲ级9例,Ⅴ级2例.其中10例患者癫痫发作减少50%以上.结论 迷走神经刺激术治疗顽固性癫痫是一种相对安全、有效的治疗方法 .     

Destruction of peripheral C-fibers does not alter subsequent vagus nerve stimulation-induced seizure suppression in rats

PURPOSE: Early animal studies of the therapeutic mechanisms of vagus nerve stimulation (VNS) suggested that seizure suppression requires maximal activation of small, unmyelinated vagal C fibers. However, effective therapeutic stimulation parameters appear to be subthreshold for these fibers in humans, and there are no clinical reports of the autonomic side effects that would be expected if these fibers were maximally activated. We report here that selective destruction of C fibers with capsaicin does not affect VNS-induced seizure suppression in rats. METHODS: Rats were pretreated with capsaicin or vehicle in three injections over a 2-day period. A cuff electrode was later implanted on the left cervical vagus nerve. Two days after surgery, VNS was given to half of the capsaicin- and vehicle-treated rats. The remaining rats were connected to the stimulator but did not receive VNS. Thirty seconds after VNS onset, seizures were induced by pentylenetetrazol (PTZ), and seizure severity was measured. Two days later, the reciprocal VNS treatment was given, and PTZ-induced seizure severity was again measured. RESULTS: VNS effectively reduced seizure severity in both capsaicin- and vehicle-treated rats as compared with their non-VNS baselines. CONCLUSIONS: These results indicate that activation of vagal C fibers is not necessary for VNS-induced seizure suppression.     

养血清脑颗粒和丙戊酸联用对戊四氮点燃癫痫大鼠的影响

目的 探讨养血清脑颗粒(YXQNG)联用丙戊酸(VPA)对戊四氮(PTZ)慢性点燃模型大鼠癫痫发作、EEG、认知功能及颞叶、海马T型Ca2+通道蛋白(Cav3.2)表达的影响. 方法 成年雄性SD大鼠40只按随机数字表法分为PTZ组、VPA组、VPA+YXQNG组、NS组,每组10只.前3组大鼠腹腔注射PTZ溶液制作慢性点燃模型,VPA组大鼠在注射PTZ前1 h给予VPA灌胃;VPA+YXQNG组除给予VPA外,注射PTZ前1.5 h给予YXQNG灌胃;NS组腹腔注射生理盐水,每天一次.8周后观察各组大鼠的行为学变化、Y型电迷宫检查大鼠的正确反应率、捕记EEG并应用免疫组化染色检测颞叶和海马Cav3.2的表达. 结果 给药8周后PTZ组大鼠全部达到完全点燃(连续3 d出现Ⅳ级发作或达到Ⅴ级发作),VPA组和VPA+YXQNG组大鼠仅出现0～Ⅱ级发作;Y型电迷宫检查结果显示VPA+YXQNG组大鼠正确反应率高于PTZ组,差异有统计学意义(P＜0.05);EEG结果显示PTZ组大鼠癫痫发作时EEG有明显异常放电,总功率高于用药前,差异有统计学意义(P＜0.05).VPA组、VPA+YXQNG组大鼠用药前后EEG总功率的差值均高于PTZ组,差异有统计学意义(P＜0.05);免疫组化染色结果显示VPA组、VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于PTZ组,VPA+YXQNG组大鼠颞叶和海马Cav3.2表达低于VPA组,差异均有统计学意义(P＜0.05). 结论 YXQNG和VPA联用能降低癫痫大鼠发作级别、改善认知功能、减少脑部异常放电并降低脑组织Cav3.2水平,有抗癫痫和脑保护作用.

Abstract：

Objective To explore the effet of Yangxue Qingnao granule (YXQNG) on seizures and cognition function of pentylenetetrazole (PTZ)-kindled chronic epileptic rats models, expression of Cav3.2 in the hippocampus and the temporal lobe of these rats, and EEG features of the rats. Methods Forty healthy adult male SD rats were equally divided into 4 groups at random: PTZ group, VPA treatment group, VPA+YXQNG treatment group, normal saline (NS)-control group (n=10). PTZ solution was intraperitoneally injected for 8 weeks to induce the kindling model in the above 3 groups except the NS-control group. VPA by intragastric administration was given to the rats in the VPA treatment group 1 h before PTZ injection; YXQNG and VPA by intragastric administration were given to the rats in the VPA+YXQNG treatment group 1.5 h before PTZ injection. Behavioral changes of the rats were observed 8 weeks after PTZ injection; accuracy rate of response of the rats were examined by electric maze test;EEG was performed; and the expression ofT-type Ca2+ channel protein (Cav3.2) in the temporal lobe and hippocampus was detected by immunohistochemical staining. Results Rats in the PTZ group appeared grade Ⅳ or Ⅴ seizures for 3 consecutive d, and rats in the VPA treatment group, VPA+YXQNG treatment group appeared grade 0-Ⅱ seizures. The accuracy rate of response of the rats in the VPA+YXQNG treatment group was significantly higher than that in the PTZ group (P＜0.05). EEG indicated that paradoxical discharge was noted in rats of PTZ group when seizures appeared, and the total power at the time was obviously higher than that before PTZ injection (P＜0.05). The D-value of total power of EEG in rats of the VPA treatment group and VPA+YXQNG treatment group before and after treatment was significantly higher than that in the PTZ group (P＜0.05). And the level of Cav3.2 in the temporal and hippocampus in rats of the VPA treatment group and VPA+YXQNG treatment group was significantly lower than that in the PTZ group (P＜0.05); as compared with that in the VPA treatment group, the expression of Cav3.2 in the temporal and hippocampus in rats of the VPA+YXQNG treatment group was significantly reduced (P＜0.05). Conclusion The combination use of YXQNG and VPA can decrease the seizure stage, the paradoxical discharge of the brain and the level of Cav3.2 in brain tissue,and improve the cognitive function of the PTZ-kindled rats, indicating that using VAP and YXQNG simultaneously can treat epileptic seizure and protect the neurons.     

Inhibition of Experimental Seizures in Canines by Repetitive Vagal Stimulation

Repetitive electrical stimulation of the canine cervical vagus nerve interrupts or abolishes motor seizures induced by strychnine and tremors induced by pentylenetetrazol (PTZ). Tremors were defined as rhythmic alternating contractions of opposing muscle groups, exerting much less force than seizure contractions. Seizures were induced by injection boluses of strychnine or PTZ at 1- to 4-min intervals until sustained muscle activity was observed electromyographically (EMG). Vagal stimulation terminated seizures in 0.5-5 s. There were prolonged periods with no spontaneous EMG activity after stimulation. The period of protection was approximately four times the stimulation period. The antiseizure actions of vagal stimulation were not altered by transection of the vagus distal to the stimulating electrode. Optimal stimulus parameters were estimated: strength, approximately 20 V (electrode resistance 1-5 omega); frequency 20-30 Hz; duration, approximately 0.2 ms. These data suggest that the antiseizure effects derive from stimulation of small-diameter afferent unmyelinated fibers in the vagus nerve. These results may form the basis of a new therapeutic approach to epilepsy.     

The mechanisms through which auricular vagus nerve stimulation protects against cerebral ischemia/reperfusion injury

Previous studies have shown that vagus nerve stimulation can improve patients' locomotor function.The stimulation of the auricular vagus nerve,which is the only superficial branch of the vagus nerve,may have similar effects to vagus nerve stimulation.However,the precise mechanisms remain poorly understood.In this study,rat models of cerebral ischemia/reperfusion injury were established by modified Longa ligation.Twenty-four hours later,7-day auricular vagus nerve stimulation was performed.The results showed that auricular vagus nerve stimulation promoted the secretion of acetylcholine,inhibited the secretion of interleukin-1β,interleukin-6,and tumor necrosis factor-α,and reduced connexin 43 phosphorylation in the ischemic penumbra and motor cortex,promoting locomotor function recovery in rats with cerebral ischemia/reperfusion injury.These findings suggested that auricular vagus nerve stimulation promotes the recovery of locomotor function in rats with cerebral ischemia/reperfusion injury by altering the secretion of acetylcholine and inflammatory factors and the phosphorylation of connexin 43.This study was approved by the Animal Use and Management Committee of Shanghai University of Traditional Chinese Medicine on November 8,2019(approval No.PZSHUTCM191108014).     

迷走神经刺激术治疗难治性癫痫(附25例报告)

目的研究迷走神经刺激术治疗难治性癫痫的适应证选择、手术方法、术后程控及疗效。方法 2009年11月~2016年7月清华大学玉泉医院癫痫中心对25例难治性癫痫患者行迷走神经刺激术,术后给予程控管理控制癫痫发作;并通过随访回顾性分析术后疗效。结果术后随访患者4个月~7年,其中癫痫发作频率减少达McHughⅠ级6例、Ⅱ级12例、Ⅲ级4例、Ⅳ级1例、Ⅴ级2例。手术前后癫痫发作频率对比,差异有统计学意义(P0.05)。结论迷走神经刺激术作为一种安全有效的辅助治疗难治性癫痫的方法,其治疗效果可以随着参数的调整和时间延长而增强,并可以一定程度改善患者的认知行为和生活质量。     

Alterations of A1 adenosine receptors in different mouse brain areas after pentylentetrazol-induced seizures, but not in the epileptic mutant mouse 'tottering'

Single and repeated Pentylentetrazol (PTZ)-induced convulsions are associated with significant changes of A1 adenosine receptors (detected using the radioligand [3H]cyclohexyladenosine, [3H]CHA) in 4 different brain areas of the mouse, namely cortex, hippocampus, cerebellum and striatum. In hippocampus and cerebellum, a rapid increase in [3H]CHA binding, by 26% and 30% respectively, was observed 1 h after a single PTZ convulsion. In striatum, on the contrary, a significant decrease by 30% in [3H]CHA binding was seen, whereas in cortex no significant change could be detected. After daily repeated PTZ convulsions, a significant increase of A1 receptors by 26% appeared also in cortex, while the changes of A1 receptors observed in the other brain areas after a single PTZ convulsion were maintained in almost the same range. All the alterations observed were due to changes of the total number of A1 receptors (Bmax) without changes in receptor affinity (Kd). A significant increase in the latency of PTZ seizure (time between the PTZ-injection and the beginning of the seizure) was also observed after repeated PTZ-induced convulsions at the time when the changes in A1 adenosine receptors were noted. Considered together, these results provide further evidence for an A1 receptor-mediated modulation of seizure susceptibility and indicate that specific brain areas may play different roles in this modulation. The binding of [3H]CHA to membranes from different cortical and subcortical areas of the epileptic mutant mouse 'tottering' was not different from that in control animals.     

Vagal and sciatic nerve stimulation have complex, time-dependent effects on chemically-induced seizures: a controlled study

Previous studies of the effects of electrical vagus stimulation on experimental seizures were without suitable controls or statistical validation, and ignored the potential role of vagally-induced hemodynamic depression on seizure expression. This study addresses these limitations. The effects of periodic left vagus nerve stimulation (LVNS) on chemically-induced seizures in rats were compared with control groups receiving no stimulation (NoS), left sciatic nerve stimulation (LSNS) and LVNS after pretreatment with methyl atropine (MA-LVNS). Stimulation followed a 30 s on-120 s off cycle over 130 min. Seizures were scored visually and the temporal variation of their probability P(s) across the stimulation cycle was measured statistically. P(s) was significantly different (P<0.01) for all groups: LSNS had the highest and MA-LVNS the lowest seizure probability; LVNS and NoS had intermediate values. While LVNS blocked seizures, it also precipitated them, explaining why its anti-seizure effect was only slightly greater than NoS. Neither LVNS nor MA-LVNS induced changes in cortical rhythms ('activation') associated with decreased P(s), unlike LSNS which increased cortical rhythm synchrony and with it, P(s). LVNS alone induced marked bradycardia and moderate hypoxemia. In conclusion, cranial and peripheral nerve stimulation have complex, time-varying effects on cerebral excitability: low frequency LSNS facilitated seizures, while LVNS both suppressed and facilitated them. The anti-seizure effect of LVNS was small and may have, in part, been due to a hemodynamically-induced deficit in energy substrates. The effects of MA-LVNS on seizure duration and P(s) raise the possibility that, in the absence of hemodynamic depression, stimulation of this nerve does not have a strong anti-seizure effect.