电刺激大鼠海马建立复杂部分性癫痫动物模型

目的　电刺激Wistar大鼠海马 (分为单侧、双侧点燃及左右侧交替点燃三组 )来建立复杂部分性癫痫的动物模型 ,探讨三种方法在建立癫痫动物模型中的可能机制。 方法　 健康Wistar大鼠 6 0只 ,随机分成三组 :单侧点燃组、双侧同时点燃组、双侧交替点燃组。按Goddard方法将电极分别植入左侧海马 (单侧 ,UK组 ) ,双侧海马(双侧 ,BK组 ;交替点燃组 ,AK组 ) ,每日接受电刺激 ,刺激条件为 :刺激强度 4 0 0 μA ,频率 6 0Hz,波宽 1ms。持续时间 1s。 结果　BK组与UK组相比 ,两者点燃率有显著差异 (10 0 %vs 5 5 % ,P <0 .0 5 )。点燃速度也显著减慢(P <0 .0 5 )。与AK组与UK组大鼠达到 5期惊厥的刺激次数 (19.36± 3.4 7)相比 ,AK组痫性发作出现的速度显著增快 (10 .85± 1.98) ,且点燃成功率为 10 0 % ,与UK组相比 (5 5 % )有显著差异 (P <0 .0 5 )。 结论　 大鼠单侧海马电刺激建立癫痫的动物模型时 ,出现点燃的延迟现象 ,表现为部分性发作和低水平的双侧海马ⅡS活动。大鼠双侧海马交替电刺激建立癫痫的动物模型时 ,表现出点燃的拮抗作用。     

双侧杏仁核同时点燃建立复杂部分性癫(疒间)模型的实验研究

目的观察双侧杏仁核同时点燃时疒间性发作的特点及出现时间,并探讨其机制。方法将40只成年雄性Wistar大鼠随机平均分为两组:双侧杏仁核同时点燃组(BK组)和单侧杏仁核点燃组(UK组)。在28d时间内,按照Goddard方法将大鼠点燃,并对结果进行对比分析。结果BK组所有大鼠在平均20.9次刺激后均出现Ⅴ级惊厥发作,点燃成功率100%,其中12只大鼠显示有自发性疒间性放电;UK组大鼠12只完全点燃,点燃成功率为60%,平均刺激次数为8.9次。两组相比双侧杏仁核点燃法可显著提高大鼠点燃成功率(P<0.01),但点燃时间明显延迟(P<0.01)。结论双侧杏仁核同时点燃可显著提高点燃成功率,并明显延缓点燃成功时间,可能与双侧点燃时神经元兴奋和抑制机制都显著增强有关。BK对点燃的致疒间机制和抗疒间药物的筛选研究提供了一种更为先进的动物模型。     

快速点燃海马杏仁核建立癫痫鼠模型

目的：快速建立实验性癫痫动物模型。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２００－６００μＡ电脉冲刺激点燃海马杏仁核。结果 电刺激可诱发痫性发作和后放电,痫性行为分为五级,后放电呈高幅棘波。在过程中,可记录到两种脑电活动：痫性脑电活动和自发性痫性脑电活动。随着电刺激次数的增多,发现Ⅱ、Ⅲ级痫性行为伴随较短的后放电时程,Ⅳ级上以痫性行为伴随较长的后放电时程。     

颈迷走神经脉冲电刺激对大鼠点燃速度及杏仁核放电的影响

目的　定量研究颈迷走神经刺激对大鼠癫痫形成速度及杏仁核放电的影响。方法　用频率 16 Hz,波宽1.0 ms,串长 10 s,串隔 7min,强度 3.0 m A的恒流脉冲电刺激 18只大鼠的左颈迷走神经 ,同时用强度 0 .4m A的恒流脉冲电诱发刺激大鼠的杏仁核。以 18只仅刺激杏仁核的大鼠作对照 ,观察其癫痫行为及杏仁核放电情况。结果　实验组有 16 / 18只大鼠被点燃 ,对照组有 17/ 18只点燃 ,组间差异无显著性 (P>0 .0 5)。比之于对照组 ,实验组点燃所需杏仁核平均刺激次数及杏仁核平均后放电阈值均显著增高 (P<0 .0 5) ,但杏仁核平均后放电时间两组差异无显著性 (P>0 .0 5)。结论　迷走神经刺激虽最终难以阻断大鼠点燃的发生 ,但可减缓大鼠点燃发生速度 ,提高杏仁核后放电阈值。其抗痫效应可能主要与提高全脑抑制水平 ,抑制痫性放电扩布有关 ,而对痫灶本身放电影响相对较小。     

癫痫动物模型点燃的研究进展

<正>癫痫作为神经系统的一种常见病,极大地影响着人类的健康和经济发展。为进一步研究癫痫,近年来建立了多种动物模型。依据研究目的、内容和方法不同,采用的癫痫动物模型也不同。按采用动物,可分为鼠模型、兔模型、猴模型、猿模型等;按诱发方式,可分为电点燃和化学点燃动物模型。癫痫点燃的动物模型是具有诱导致痫和自发性发作优点的致痫模型。本文将对点燃的现象、概念、点燃方法、可被点燃的动物、点燃的电生理基础机制等进行综述。1.点燃的概念点燃(kindling)原始概念是指通过重复不变的亚抽搐剂量的电刺激,导致癫痫活动的强度逐渐增加,最终出现全身性癫痫发作称为点燃。此外,用化学和药物周期性的亚抽搐剂量稳定刺激也能逐渐诱发出癫痫,并且癫痫的程度逐渐加重,这个过程也称之为点燃。点燃目前被公认为是一种理想的癫痫动物模型,其致痫性增高具有永久的保留能力,较好地模拟了人类癫痫的进行性发展和长期反复的自限性发作形式。目前,主要的癫痫模型有化学点燃、脑内点燃、光或电点燃、脑组织片点燃等模型。后三种致痫方法对动物或实验设备要求高。脑内点燃或脑组织片点燃因损伤脑组织不宜进行脑生化研究。化学点燃致癫痫模型因不损伤脑组织,实验设备要求简单,结果稳定,已被广泛应用于抗癫痫药物敏感性和耐药性实验以及癫痫基础研究,特别适用于神经生物化学和形态结构方面的研究。Wada将点燃过程分为6个阶段(1)同侧面部抽搐;(2)两侧面部抽搐;(3)点头;(4)对侧前肢出现阵挛.并且头向对侧旋转;(5)站立时出现阵挛性跳跃(6)摔倒,并全身抽搐(强直-阵挛发作)。在试验中,一旦动物出现摔倒伴全身性抽搐,就被认为已制成点燃模型。这种作用是持续的,动物点燃后停止刺激12个月,再次用原第一次的剂量刺激,仍能出现摔倒伴全身抽搐。目前尚没有方法可逆转点燃作用。点燃的癫痫发作的几个特征支持其作为人类癫痫发作的模型。第一,点燃的癫痫发作行为类似于人类复杂部分性癫痫发作伴继发全身强直-阵挛发作;第二,点燃癫痫发作期间的脑电图异常类似于人复杂部分性癫痫发作期间杏仁核和海马结构电极描记的结果;第三,发作间期脑电图都可记录到棘波;第四,抗癫痫药物(苯妥英钠除外)能够有效阻止点燃。     

大鼠海马快速点燃模型的建立及机制研究

目的：建立大鼠海马快速点燃模型并对其机制进行初步探讨。方法：制备大鼠海马快速点燃模型；观察经典抗杏仁核点燃药物对该模型的影响；观察大鼠海马快速点燃模型和大鼠杏仁核点燃模型海马CA_3区和皮层区c-fos蛋白的表达情况及蛋白抑制剂对其表达的影响。结果：大鼠海马快速点燃模型点燃成功率与刺激参数有关；苯巴比妥20，50mg·kg~1 及地西泮2，5mg·kg~(-1)对大鼠海马快速点燃ADD和Racine＇s分级有抑制作用(P＜0．05)；与正常组比较，海马快速点燃大鼠和杏仁核点燃大鼠海马CA_3区、大脑皮层c-fos免疫阳性细胞增多(P＜0．05)，在蛋白抑制剂作用下，海马c-fos免疫阳性细胞减少，但仍比正常组高(P＜0．05)。结论：大鼠海马快速点燃成功率与刺激参数具有相关性；传统抗点燃药物具有抗海马快速点燃作用；大鼠海马快速点燃模型c-fos蛋白在不同脑区和核团的免疫阳性表达细胞增加。     

尼莫地平对戊四氮慢性点燃癫痫大鼠行为及脑电图的影响

目的:探讨尼莫地平(nimodipine,NIM)对戊四氮(Pentylenetetrazole,PTZ)慢性点燃癫痫大鼠行为及脑电图的影响。方法:64只动物随机分为正常对照组(A组)、PTZ单纯致痫组(B组)、NIM1.25mg/kg干预组(C组)、NIM2.5mg/kg干预组(D组),通过腹腔注射PTZ建立慢性癫痫动物模型,观察大鼠行为、脑电图及海马组织学改变。结果:腹腔注射NIM可以明显抑制大鼠的痫性放电,减小其痫性发作级别,与正常对照组相比重型发作率明显降低(P<0.01),此外,NIM还能减轻海马的损伤程度。结论:NIM在PTZ慢性点燃癫痫大鼠模型中不仅具有抗惊厥作用,还能减轻海马的损伤程度。     

戊四氮点燃过程中大鼠海马胶质细胞增生和突触重建的研究

目的探讨戊四氮点燃过程中海马胶质细胞增生及突触重建与慢性癫痫发病机制的关系。方法大鼠随机分为对照组、非药物干预组(戊四氮35mg/kg,腹腔注射,每日一次)和药物干预组(苯巴比妥30mg/kg,戊四氮35mg/kg,均为腹腔注射,每日一次)。采用免疫组织化学方法观察胶质原纤维酸性蛋白(GFAP)和神经细胞粘附分子(NCAM)表达水平。结果非药物干预组大鼠注射戊四氮后在行为学未出现惊厥,脑电图未出现痫性放电的点燃前潜伏期内,出现突触重建和胶质细胞增生,以海马CA3区、门区明显,与对照组比较,有显著性差异(P<0.05);与药物干预组对应时间点比较,亦有显著性差异(P<0.05)。结论大鼠注射戊四氮后引起反应性胶质细胞增生和神经元可塑性改变,可能与形成异常神经元放电环路,最终诱发癫痫发作有关,苯巴比妥可抑制异常神经网络的建立,预防癫痫发生。     

大鼠电点燃模型海马可塑性改变及其致病机制

目的观察大鼠海马快速电点燃模型海马结构的可塑性改变,探讨其与癫痫发作的关系.方法24只Wistar大鼠右侧海马植入双极电极,平分为2组：对照组和电刺激组,观察动物发作行为,记录脑电发放,行右侧海马部尼氏体、胶质纤维酸性蛋白（GFAP）和脑源性神经营养因子（BDNF）染色.结果与对照组相比,癫痫发作组出现明显的神经元缺失、胶质细胞增生和BDNF表达上调.结论本模型中海马结构的可塑性改变可促进癫痫发作,是慢性癫痫得以维持和发展的结构基础.     

点燃鼠痫性发作对神经元凋亡的影响

目的 观察点燃大鼠痫性发作对神经元凋亡的影响。方法 用ＩＳ－Ⅱ型智能刺激仪点燃大鼠致痫性反复发作,并用原位末端标记染色法显示点燃后不同时期垢凋亡细胞,结果 发现痫性发作后海马、杏仁核、大脑皮质、丘脑、小脑神经元凋亡明显增多。其海马ＣＡ３、ＣＡ１区凋亡细胞在２４小时最多,且持续３周以上。结论 痫性发作可使痫灶局部和远隔痫灶的神经元凋亡,此可能与顽固性癫痫的成因有关。     

Simultaneous kindling of the bilateral hippocampi: an advanced model for epilepsy research

PURPOSE: To examine whether simultaneous kindling of bilateral hippocampi [bilateral kindling (BK)] could accelerate the achievement of seizures by the breakdown of kindling antagonism or decelerate the achievement of seizures by its enhancement. METHODS: The hippocampi of 17 adult rabbits were simultaneously kindled bilaterally according to Goddard's method. RESULTS: All animals developed stage 5 convulsions after a mean of 28 stimulations. Six animals showed spontaneous seizure discharges. Afterdischarge duration increased abruptly during the early period of kindling, but thereafter it gradually progressed. Chronological analyses of interictal discharges (IIDs) demonstrated that simple as well as complex types of IIDs increased their frequencies during BK. CONCLUSIONS: Compared with unilaterally kindled animals, the BK procedure significantly increased the percentage of animals that successfully kindled (100% vs. 59%; p < 0.01), whereas it significantly decelerated the kindling progression (28 days vs. 19 days; p < 0.02). We conclude that the BK procedure represents potentiation of both excitatory and inhibitory mechanisms. Although the reason why such an antagonistic relationship between them breaks down is still unknown, the BK provides an advanced animal model to study the pathogenic mechanisms of kindling and to screen anticonvulsants.     

Epileptogenesis induced by alternate-site kindling in bilateral hippocampi

PURPOSE: Alternate-site kindling (AK), which has been known to induce so-called kindling antagonism, was performed in the bilateral hippocampi to reveal neural mechanisms underlying hippocampal kindling. METHODS: Ten adult rabbits were used. Daily kindling stimulation consisted of a 1- s train of 50 pulses (pulse duration, 1 ms) of 80 to 200 microA (base-to-peak), which was higher than the afterdischarge (AD) threshold. The concurrent alternating stimulations were delivered to the right and left hippocampus once every 24 h. RESULTS: All animals developed a stage 5 convulsion with a mean of 28.1 +/- 3.3 (mean +/- SEM) stimulations. The right and left hippocampus received 14.8 +/- 1.7 and 14.6 +/- 1.6 stimulations, respectively. Behavioral stages induced by stimulation of the right or left hippocampus evolved to generalized seizures along a similar course. Kindling antagonism was not observed. The two sides showed similar increases in AD duration, and similar chronologic changes in interictal discharge (IID) frequency. Simple A-type IID and complex types of IID appeared at higher rates, whereas simple B-type IID remained at a relatively low level. CONCLUSIONS: The present AK procedure did not induce kindling antagonism, but it induced progression of kindling manifestations. The origin of simple B-type IID is known to be in the contralateral side, and its intracellular counterpart corresponds to a sequence of small depolarization followed by large hyperpolarization, suggesting that plastic changes in the feed-forward inhibitory system play an important role in hippocampal kindling.     

Spectral analysis of bilateral or alternate-site kindling-induced afterdischarges in the rabbit hippocampi

Kindling is one of the popular animal models of temporal lobe epilepsy. In the present study following the previous results obtained using unilateral hippocampal kindling (UK), we performed spectral analysis of bilateral or alternate-site kindling-induced afterdischarges (ADs) in the rabbit hippocampi. Eight and ten adult rabbits were used for bilateral kindling (BK) and alternate-site kindling (AK), respectively. Kindling stimuli consisted of a train of biphasic pulses (1ms duration each) of 50Hz for 1s, with suprathreshold intensity for AD. The stimulations were applied simultaneously to the bilateral hippocampi in the BK and were delivered to the right and left hippocampus once every 24h in the AK. Motor responses were classified into five stages according to the conventional criteria. All animals in BK as well as AK developed stage 5 convulsions. This contrasts to the result of UK (kindled: 50%; incomplete: 50%). We normalized power spectral density (PSD) and monitored the changes in the proportion of lower frequency band component (LFB: 0-9Hz) and the higher frequency band (HFB: 12-30Hz). BK animals showed a significantly large decrement (0.5 times, p<0.01) in LFB component at the final stage compared to the initial stage, but a very large increment (4.7 times) in HFB component. Likewise, AK animals exhibited a significantly large decrement (0.6 times, p<0.01) in LFB component at the final stage, but a very large increment (3.6 times) in HFB component. Correlation analyses were performed between the HFB component and AD duration, interictal discharge frequency, and behavioral stages during kindling progression. Very strong positive correlations were found in both kindling animals. Chronological spectral analysis of seizure discharges, resulting in a pattern of LFB decrement accompanied by HFB increment, is a convenient tool to investigate epileptic disorders and diagnose epileptic states.     

尼卡地平对戊四唑化学性点燃的拮抗作用

目的:研究二氢吡啶类钙通道阻滞剂尼卡地平对大鼠戊四唑(PTZ)化学性点燃(kindling)的拮抗作用。方法:建立大鼠PTZ化学性点燃模型,观察尼卡地平对PTZ点燃发展进程和点燃发作的影响。结果:尼卡地平2mg·kg~(-1)ip明显抑制PTZ点燃的发展进程(P<0.001);2～20mg·kg~(-1)ip显著抑制PTZ点燃发作(P<0.01)。并呈量效关系;尼卡地平20mg·kg~(-1)ip对小鼠PTZ惊厥有保护作用(P<0.01)。结论:尼卡地平对PTZ化学性点燃的发展和发作有拮抗作用。     

新型抗癫痫药唑尼沙胺对点燃的影响

目的研究唑尼沙胺对大鼠杏仁核点燃及戊四唑(PTZ)化学性点燃模型的抗癫痫作用。方法建立大鼠杏仁核电刺激点燃、化学性点燃模型,探讨唑尼沙胺的抗点燃作用;测定唑尼沙胺对小鼠最大电休克的影响。结果唑尼沙胺50~200mg·kg-1ig可抑制大鼠杏仁核点燃发作,降低Racine's分级唑尼沙胺50,100mg·kg-1ig抑制PTZ化学性点燃发作,降低Ono分级(P<0.01)与OnoⅣ级发作百分率(P<0.01)。ZNS10.0mg·kg-1ig降低小鼠最大电休克诱发的,惊厥发生率(P<0.01)。结论唑尼沙胺对点燃发作具有拮抗作用。     

Interactions between chemical and electrical kindling of the rat amygdala

Holtzman rats were implanted with a chemitrode into the left basolateral amygdala, which could then be stimulated electrically (400 μA, 1 s, AC) or chemically by injection of carbachol (1 μl, 2.7 nmoles, sterile, isotonic). Group A received a daily injection of carbachol and developed kindled seizures. Group B received carbachol mixed with equimolar atropine, which blocked seizures and kindling. After 20 injections, both groups were stimulated electrically once a day and kindled at similar rates. Two additional groups received electrical or sham stimulation, followed by carbachol kindlind. No transfer effects were observed. Four additional groups received 27 nmoles of atropine through the chemitrode, followed 15 min later by electrical stimulation, sham stimulation, carbachol injection or saline injection, respectively. Atropine completely blocked carbachol kindling but did not alter the rate of electrical kindling. No difference in the number of QNB binding sites was observed in the amygdala of rats sacrificed two weeks after full electrical kindling. The lack of interaction between electrical and carbachol kindling and the failure of atropine to block electrical kindling of the amygdala suggest that the activation of local muscarinic synapses, while essential for carbachol kindling, is not required for electrical kindling of the rat amygdala.     

Neuropathological profile of the pentylenetetrazol (PTZ) kindling model

ABSTRACT

Introduction: There are three phases of seizure developing in pentylenetetrazol (PTZ)-induced kindling animal model: (i) pre-kindling phase; (ii) kindling phase or after animals are fully kindled; (iii) post-kindling phase with non-provoked spontaneous recurrent seizures. The aims of this review were to summarize the progress over time of the electroencephalographic features and neuropathological alterations in kindled PTZ treated animals.

Materials and methods: Keywords relevant to PTZ kindling were used to a guide a literature search on Pubmed, Medline and Cochrane Library.

Results: Clonic seizures induced PTZ at kindling phase led to a strong c-Fos expression in the hippocampus. Although, decline hippocampal neuron and metabolism disturbances were detected at pre-kindlig phase. Repeated PTZ induced seizures alter the GABA-mediated inhibition and glutamate-mediated excitation, which may contribute to increased seizure susceptibility. Similar to chemical animal models such as the pilocarpine and the kainic acid models, mossy fiber sprouting, hippocampal damage, and glucose hypometabolism had been seen after PTZ induced seizures.

Conclusion: PTZ kindling model may improve understanding of the seizures development provided that the differences existing between the phases of kindling model are taken into account.     

Chemical kindling with Met-enkephalin and transfer between chemical and electrical kindling

The role played by Met-enkephalin (ME) in epileptic seizures was investigated, using 57 ME kindled rats and 10 saline injected control rats. Repeated microinjection of 10 micrograms ME into the right amygdala (AM) of male Wistar rats led to development of generalized convulsions. One week after the completion of ME kindling, 1 or 2 electrical stimulations (200-400 microA, 60 Hz, 1 sec) of the right AM of ME kindled rats resulted in generalized convulsions in 5 rats. The duration of after-discharge (AD) in the first generalized convulsion induced by electrical AM stimulation in the ME kindled rats was significantly longer than that in the first generalized convulsion induced by electrical stimulation in the saline treated control rats (P less than 0.05). One week after the completion of ME kindling, naloxone (10 or 20 mg/kg, i.p.) given 10 min before the infusion of ME into the other 3 ME kindled rats attenuated both convulsive behavior and electrographical seizures. With the progress of convulsive behavior, the frequency of wet-dog shakes (WDS) tended to decrease and was significantly lower after ME injection in the first stage 5 seizures than after the first ME injection (P less than 0.01). These results strongly suggest that ME has a potent epileptogenic effect on the rat brain which is caused by the opioid receptors. There are some differences between chemical kindling with ME and electrical kindling as indicated by the development of the AD duration and the WDS frequency.     

Chemical kindling by muscarinic amygdaloid stimulation in the rat

507 Holtzman rats received injections, through chemitrodes chronically implanted into the basolateral amygdala, of 0.2–1 μl of sterile isotonic solution containing nanomolar quantities of cholinergic muscarinic agonists and/or antagonists. The bulk of the injected solution diffused only a short distance as judged by autoradiography. Once daily injections of 2.7 nmoles of carbamylcholine, an initially subconvulsive dose, kindled the progressive development of epileptic seizures similar to those seen in electrical amygdaloid kindling. This response was dependent on dose and on interstimulus interval, and once established persisted at least 8 weeks without further stimulation. Spontaneous seizures were observed in some fully kindled animals. No kindling-specific changes were seen by light microscopy. Muscarine (3 nmol) and the active (+), but not the inactive (−), isomer of acetyl-β-methylcholine also kindled seizures. The action of (+)-acetyl-β-methylcholine was potentiated by the cholinesterase inhibitor physostigmine. The muscarinic antagonists atropine and quinuclidinyl benzylate (QNB) blocked kindling by carbamylcholine or muscarine. Atropine, QBN and scopoamine greatly reduced agonist-induced seizures in previously kindled rats. Highly significant transfer effects were observed between muscarinic agonists, i.e. muscarine-kindled rats had widespread seizures on their first carbamylcholine exposure and vice versa. Kindled animals had a lowered seizure threshold for muscarinic agonists. Dibutyryl cyclic GMP produced seizures but no kindling. Those results demonstrate that in this model the stimulation of a group of muscarinic cholinergic synapses is both necessary and sufficient to induce a kindled state characterized by both evoked and spontaneous seizures, and support the view that epilepsy can be acquired and expressed transsynaptically.     

Kindled Amygdaloid Seizures in Rats Cause Immediate and Transient Increase in Protein Kinase C Activity Followed by Transient Suppression of the Activity

Summary: Protein kinase C (PKC) activity in hippocampus and amygdala was measured during kindled seizures and 30 rnin, 3, 24, and 80 h, and 2 weeks after seizures in amygdaloid-kindled rats. Shamperated rats not subjected to kindling were used as controls. During kindled seizures, membrane-bound PKC activity in bilateral hippocampi was significantly increased, with a slight reduction in cytosolic PKC activity, but there was no change in either membrane-bound or cytosolic PKC activity in bilateral amygdaIa. Thirty minutes after seizures, PKC activity in both fractions was significantly increased in bilateral hippocampi and amygdala. Three hours after seizures, PKC activity in both fractions was markedly decreased in bilateral hippocampi. In bilateral amygdala, a similar and significant decrease in membrane-bound PKC activity was noted, with no marked change in the cytosolic fraction. Twenty–four hours after seizurs, a significant decrease in membrane–bound PKC activity in bilateral hippocampi and amygdala was again noted, although cytosolic PKC activity was unchanged. Fortyeight hours after the seizures, PKC activity in both fractions had returned to control levels. Two weeks after the last seizure, there was no significant change in PKC activity in either fraction in any region, except for a slightincrease in membrane–bound PKC activity in unilateral hippocampus contralateral to the kindled arnygdala. These results suggest that kindled amygdaloid seizures cause an immediate and transient increase in PKC activity in limbic structures, followed by suppression of enzyme activity, and that PKC in hippocampus responds to kindled seizures more readily and preferentially than it does in amygdala. Examination of the direct effect of kindled seizures on PKC activity is important for understanding of the relation between kindled phenomena and PKC in limbic structures.