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Kindling is the progressive development of intense temporal lobe and generalized seizures induced by repeated subconvulsive electrical stimuli applied to certain brain structures.1 Kindling is considered an animal model of human complex partial (temporal lobe) seizures2, 3 and substantial evidence suggests that the amygdala is involved in temporal lobe epilepsy.4,5 The amygdala is one of the areas most readily kindled6-8 and the basolateral nucleus of the amygdala is a brain area commonly selected to induce kindling.8-10 [ABSTRACT FROM AUTHOR]

The term "neural plasticity" was first used by Minea1 to indicate the metamorphic phenomena of sensory neurons caused by the compression and transplantation of ganglia into various organs. More comprehensively, it describes the functional or structural reorganisation that occurs at molecular, cellular, or circuit level within the central nervous system as a consequence of physiological or pathological activities or lesional insults. When this happens during development, it may alter the developmental programme, but it can also cause rearrangements of an already mature neural structure. [ABSTRACT FROM AUTHOR]

In the long-term clinical course of epilepsy, there is an increased incidence of the development of schizophrenia-like paranoid symptoms, such as delusion and hallucination. The prevalence of this epileptic psychosis appears to be about 7-11%, which is much higher than in the general population.22,37 Since some patients with epileptic psychosis show an inverse correlation between the presence of epilepsy and the psychosis, this phenomenon was has been labeled "forced normalization" or "alternative psychosis" (see review of Krishnamoorthy and Trimble18). Slater et al.,30 on the other hand, reported that the emergence of epileptic psychosis was related to the duration of epilepsy and to the brain damage, and was linked to temporal lobe epilepsy (TLE). [ABSTRACT FROM AUTHOR]

Temporal lobe epilepsy, the most common form of human epilepsy,1 is most often associated with hippocampal sclerosis (HS), the most common epileptogenic lesion.2 This condition is referred to as mesial temporal lobe epilepsy (MTLE) with HS.3 Perhaps in recognition of the importance of MTLE with HS as a major health burden worldwide, a large percentage of research on epilepsy now utilizes animal models of this disorder. Whereas kindling was the most popular model of MTLE during the 1970s and' 80s, it has been largely replaced in recent years by chronic post status epilepticus models induced by excitotoxic substances such as kainic acid (KA) and pilocarpine (Pilo), or tetanic hippocampal stimulation to produce self-sustained status epilepticus (SSSE).4 This chapter will briefly review MTLE with HS and examine the strengths and weaknesses of these various experimental models for investigating mechanisms underlying this human condition. [ABSTRACT FROM AUTHOR]

While kindling emphasizes a progressive process underlying partial-onset epilepsy, recognition of its variation, not only regarding ontogenesis and phylogenesis but also regarding the role of predisposition, will expand its clinical relevance. Nearly 70 years ago, Watanabe1 showed that electrically induced generalized convulsions in dogs led to pathological changes similar to the Ammon's horn sclerosis found in the brain of patients with epilepsy. In his paper he described a remarkable individual variation in susceptibility, not only for development of the pathology but also for spontaneous seizures and status epilepticus. Variation of kindling results among five primate species, i.e., photosensitive Papio papio (Pp, Senegal) and Papio cynocephalus (Pc, Ethiopia); non-photosensitive Papio hamadryas (Ph, Kenya), Macaca fuscata (Mf, Japan) and Macaca mulatta (Mm, India), have been reviewed from a similar perspective. The technical protocol including once-a-day kindling stimulation was identical in all the species. Since the amygdala (AM) was the only brain site where all five species were kindled, this discussion will be largely, if not completely, centered on AM kindling. [ABSTRACT FROM AUTHOR]

Engel: I was really pleased to see all the applications of kindling and the study of behavior, and I wondered if anybody looked at lateralized effects. I don't mean left vs right, which some of you talked about. Rather, did you ever see, for example, hyperreactivity that was just unilateral. I ask this because, many years ago, we looked at the cat with intrahippocampal kainate to produce defensive rage. When the animal started having spontaneous seizures, they had defensive rage when you approached them, but only when you approached them contralateral to the epileptic hippocampus. If you approached ipsilateral they rubbed up against you and purred. I always wondered whether we should be looking for this in our patients, for unilateral behavioral changes. Has anyone ever looked at that? [ABSTRACT FROM AUTHOR]

Although deep brain electrical stimulation has been studied as a therapy for epilepsy since the 1930's1 we have still not determined the optimal sites for delivery of the stimulus or the most effective stimulus parameters. Superimposed on these questions is the requirement that the ultimate therapeutic stimulation needs to be safe and not interfere with normal brain function. Given the recent success using deep brain stimulation to treat movement disorders2 and the limited success of vagus nerve stimulation for epilepsy,3 there has been a renewed interest in deep brain stimulation as a therapy for epilepsy. In many ways the clinical use of deep brain stimulation is moving faster than the basic research, which usually precedes and is the often the basis for the development of new clinical therapies. Nevertheless, a number of laboratories are using in vitro and in vivo animal models to develop deep brain electrical stimulation as a therapy for epilepsy. [ABSTRACT FROM AUTHOR]

For millennia there has been interest in the potential therapeutic effects of marijuana (cannabis), including its potential antiepileptic effects. A flurry of research on cannabis and seizures occurred in the 1970s, when purified tetrahydrocannabinol (THC) became available for research. The results demonstrated that a variety of seizures, including kindled seizures can be suppressed by THC, but typically at toxic doses.1-3 It was also reported that prophylactic administration of THC can delay limbic kindling in rats2 and cats.3 In contrast, other studies that received less attention described proepileptic or proconvulsant effects of a variety of cannabinoids, including THC.4-6 Because of a lack of knowledge about the mechanisms of cannabis's effects oh the brain, research on cannabis and epilepsy declined to a very low level in the 1980s. [ABSTRACT FROM AUTHOR]

In recent years, our laboratory has been using the kindling model in a search for new drugs effective against intractable epilepsy. In this chapter, I would like to discuss (1) intractable epilepsy; (2) the limbic kindling model and how it should be used in pharmacological studies related to complex partial seizures; (3) our approach to drug discovery; (4) our experiments with deoxycorticosterone and its metabolites; and (5) our experiments with progesterone and its metabolites. [ABSTRACT FROM AUTHOR]

Although several new antiepileptic drugs (AEDs) have been launched during the last two decades, pharmacoresistance of epilepsy is still a major problem in clinical neurology. About 30% of all epileptic patients do not adequately respond to drug treatment.1 In adults, temporal lobe epilepsy (TLE) with complex-partial seizures has the poorest prognosis with up to 70% of the patients being resistant to treatment with available AEDs.2 Although several risk factors for intractability have been identified, the mechanisms underlying intractable epilepsy have not been fully enlightened. Recent data gave evidence that pharmacodynamic mechanisms, i.e., changes in drug targets (target hypothesis),3 as well as pharmacokinetic mechanisms, i.e., a local decrease in brain access of AEDs mediated by overexpression of multidrug transporters (multidrug transporter hypothesis),4 may be involved. Investigations in animal models of pharmacoresistant epilepsy are helpful to increase the understanding of the underlying basis of intractability, i.e., to further substantiate the existing hypotheses, to define further mechanisms, and to examine how different mechanisms coact. Unfortunately, there are only few animal models of pharmacoresistant epilepsy. One of the most extensively characterized animal models in this respect is a pharmacoresistant subgroup of amygdala-kindled Wistar rats. [ABSTRACT FROM AUTHOR]

A unique form of pharmacodynamic tolerance develops when effective anticonvulsants are given as pre-treatment before once-daily amygdala-kindled seizures in animals.1,2 This loss of efficacy (i.e., tolerance) is contingent upon the drug's administration before, but not immediately after, the kindling stimulation.3-6 This form of tolerance can be reversed after a period of seizures off anticonvulsants, or even continuing to give anticonvulsants on a once-daily basis but after a fully developed kindled seizure has already occurred. [ABSTRACT FROM AUTHOR]

Conventional kindling experiments appear ideal for generating inadvertent conditioned effects: A variety of stimuli (e.g., removal from the home cage, attachment to the stimulation lead, and placement in the stimulation environment) are repeatedly presented to the animal prior to each stimulation and convulsion. We recently demonstrated that the stimulation environment can have a major impact on both kindled convulsions and interictal behaviour. Rats received periodic stimulations to the basolateral amygdala (BA) in one conditional environment (CS+) and an equal number of sham stimulations (the stimulation lead was attached but no current was delivered) in a second environment (CS−) in a quasirandom sequence. As kindling progressed, the rats became more defensive in the CS+ environment than in the CS− environment; and, when they were finally stimulated in the CS− environment, their convulsions were substantially less severe than in the CS+ environment.1 Furthermore, the kindled rats preferred the CS− environment to the CS+ environment in a subsequent conditioned place preference test. [ABSTRACT FROM AUTHOR]

A number of interictal behavioral co-morbidities accompany temporal lobe epilepsy. These co-morbidities range from fear and anxiety to depression and memory loss. For many patients, these behavioral disturbances pose a greater problem than the seizures themselves, because they can disable patients to the point where they cannot work or sustain normal relationships. Surprisingly, relative to the seizures themselves, these behavioral problems have received little experimental attention. [ABSTRACT FROM AUTHOR]

Epilepsy is a chronic disorder defined by the recurrence of spontaneous seizures affecting ∼2% of the population in North America.1 There are a variety of distinct subtypes of the disorder with the most common, temporal lobe epilepsy (TLE), accounting for about 55% of all cases.1, 2 While the seizures themselves can be significantly debilitating, the clinical impact of TLE is exacerbated by the fact that about half of all sufferers exhibit serious disturbances of affect and/or memory function.3-6 At present, the mechanisms of these TLE-associated psychological impairments are unknown and, although recent studies have begun to explore the potential effectiveness of behavioral interventions,7,8 there is no treatment currently available. Consequently, these problems are often neglected clinically and have a significant adverse effect on patient quality of life.9 There is a clear need, then, for research to provide a better understanding of the bases for epilepsy-associated psychological disturbances and to develop effective treatment strategies. Clinical studies, however, are challenging because of the large number of potentially relevant but difficult to control variables. Thus, progress relies heavily on work with suitable animal models. The present chapter reviews studies on one such model — kindling in rats, and describes characteristics of spatial memory changes in this model, their relation to kindling-related variables, and potential mediating mechanisms. [ABSTRACT FROM AUTHOR]

The most commonly agreed upon forms of affective psychopathology accompanying seizure disorders in humans are depression and anxiety.1,2 A variety of factors impact on affect in human epileptics, complicating determination of the contribution of epileptic pathophysiology to psychopathology. Factors include family history, medication, psychosocial factors and premorbid psychiatric condition1. Limbic kindling has been proposed as a model of complex partial seizure disorder with secondary generalization.1,3-5 Kindling of limbic foci produces lasting changes in animal behavior, including anxiety like behavior (ALB)1,6-9 and cognition.10 The lasting changes in ALB produced by kindling are consistent with the idea that seizures change affective behavior. Nevertheless, the nature of behavioral change produced by kindling is also complicated by a number of clinically relevant factors. [ABSTRACT FROM AUTHOR]

Neuropeptide Y (NPY)-mediated neurotransmission undergoes plastic changes during hippocampal or amygdaloid kindling in rats as shown by changes in peptide cellular expression and distribution, its release and receptor subtype plasticity (for review see 37, 51). Electrophysiological and pharmacological evidence in in vitro and in vivo models of seizures indicate that NPY has predominant inhibitory actions on excitatory glutamate-mediated neurotransmission and it displays anticonvulsant properties in acute models of seizures.37, 51 Information about its functional role in epileptogenesis is more limited although recent evidence points to an antiepileptogenic action of this peptide.4, 38 In this chapter, we will review the available evidence concerning the functional role of endogenous NPY in kindling and we will address the contribution of its receptor subtypes in mediating its antiepileptogenic effects providing novel findings on the involvement of Y2 and Y5 receptor subtypes. [ABSTRACT FROM AUTHOR]

Epilepsy is a common and frequently devastating neurological disorder, affecting approximately 1% of the population. Among the diverse forms, limbic epilepsy (synonyms include complex partial epilepsy, temporal lobe epilepsy, psychomotor epilepsy) in particular is the most devastating in adults for three reasons: (1) it is common, accounting for approximately 40% of all cases of adult epilepsy; (2) limbic seizures are often quite resistant to available anticonvulsant drugs;1 and (3) the attacks induce impairment of consciousness, thereby limiting driving, maintaining employment, etc. Therapy is only symptomatic in that available drugs inhibit seizures in some individuals but do not modify the disease itself. [ABSTRACT FROM AUTHOR]

Graham Goddard1 initially introduced kindling as a model for memory. Although most frequently utilized as an epilepsy model, particularly for temporal lobe epilepsy, kindling is occasionally used as a model for drug-induced plasticity, slowly developing neuropathologies other than epilepsy, and a variety of structural reorganizations of brain circuitry.2,3 Since our interest in the kindling phenomenon (and other models of epilepsy) is largely driven by our interest in neural plasticity, we have chosen to focus on kindling-induced neuronal reorganization. These kindling-induced effects may not have much relevance for epilepsy, but they are themselves interesting and potentially important phenomena and provide an excellent model for the study of mechanisms of activity-dependent neural growth. [ABSTRACT FROM AUTHOR]

Galanin is a 29 aminoacid residue neuropeptide (30 amionoacids in humans) widely distributed throughout central nervous system and intestines1,2 that has been shown to be involved in regulation of numerous processes; such as feeding, nociception, nerve regeneration, memory, neuroendocrine release, intestine secretion and contractility (see 2). In the brain, galanin is normally present in cholinergic and noradrenergic neuronal populations of the medial septum and locus coeruleus, respectively.3-10 It is transported and subsequently released by the extensive axonal projections of these neurons into a wide range of forebrain regions, including the hippocampus. In addition, intrahippocampal colchicine administration, which blocks fast axonal transport and mitosis, produces scattered galanin-immunoreactive neurons and glial cell bodies in the hippocampus.2,11 Galanin acts via 3, so far identified, distinct G-protein-linked receptor subtypes: GalR1, GalR2 and GalR3.12-16 Similar to galanin, GalR1 and GalR2 (but not GalR3) mRNAs are abundantly expressed in many brain areas.17,18 The detailed mapping of galanin mRNA, its immunoreactivity and binding sites demonstrated that for the most part mRNA expression matches with observed immunoreactivity in the cells, and that receptor binding sites correlate well with galanin-immunoreactive fiber bundles in various regions of the rat brain (for details see2). Activation of GalR1 and GalR3 has been shown to inhibit adenylyl cyclase, decrease cAMP concentration, and open G-protein-coupled inwardly rectifying K+ channels. GalR2 stimulates phospholypase C and PKC action.13,19,20 [ABSTRACT FROM AUTHOR]

Knowledge of the cellular and molecular mechanisms underlying the various forms of epilepsy could drive the search for new drugs and lead to improved therapies. The proposal of J.H. Jackson, put forward more than a century ago, that seizures are caused by "occasional, sudden, excessive, rapid and local discharges of gray matter" still provides a useful framework for research. [ABSTRACT FROM AUTHOR]

Application of the newly developed tools of proteomics analysis to the brain is still at an early stage of development. Primary application of 2D gel electrophoresis coupled with mass spectrometry based protein identification has been primarily directed at analyzing whole brain proteomes. As has been recently reviewed,1 this has led to the identification of a number of the more abundant brain proteins but has yet to focus on the important functional sub-compartments of the neuron (e.g., the synapse) or to probe for potential changes in disease states. This, in part, reflects a major limitation of protein profiling: the inherent complexity of proteomes even of subcellular compartments. We have begun to establish 2D gel maps for rat hippocampal synaptosomes and sub-fractions (synaptosol, plasma membrane and vesicle fractions) in both the resting and depolarized state. In this chapter we demonstrate how this technique can be applied to the study of kindled epilepsy. [ABSTRACT FROM AUTHOR]

Kindling is a phenomenon by which the periodic application of an initially subconvulsive electrical stimulus results in a progressive development of epileptiform activity, culminating in the manifestation of generalized seizures in response to the stimulus. Once the animal is kindled, the enhanced state of excitability is permanent1-5 Kindling stimulation can produce a great number of effects, any of which could contribute to the development of an epileptogenic state. Many studies have shown interactions between kindling and neurotransmitter systems,6-11 second messengers,12-14 and ion channels.15-17 Histological studies with light and electron microscopy also reveal neural structure changes and mossy fiber sprouting in kindled animals.18-20 Thus, kindling produces both structural and chemical changes, many of which are associated with or result from changes in gene expression. This chapter focuses on changes in regulator of G-protein signaling (RGS), Ca2+/calmodulin-dependent protein kinase II (CaMK II) gene expression, and long-lasting changes in gene expression in kindling. [ABSTRACT FROM AUTHOR]

The view that genetic mechanisms underlie many forms of epilepsy is widely accepted.1 Thus, genetically-derived models of epilepsy can serve as important vehicles to study the mechanisms of epileptogenesis,2 particularly if they can isolate underlying factors that are uncontaminated by a recent history of seizure activity. [ABSTRACT FROM AUTHOR]

Schwartzkroin: A couple of comments related to Dr. Sutula's presentation: First, I really applaud you on what I think is a provocative presentation. So let me be provocative in response and say that I think that it is dangerous to be searching too hard for common mechanisms, that that's the way the field got in trouble at the very beginning when we started looking for a silver bullet that would explain everything, and that the field really exploded when we understood that epilepsy wasn't epilepsy, it was the epilepsies. As an outsider to a kindling conference, I would say that kindling isn't kindling, that these are in fact multiple and potentially very different kinds of phenomena that people are dealing with, and that there is kind of a common tool that they use to study them. I would draw the analogy to the advent of slice technology: slice is a technique. Is there a entity called kindling, or in fact is as, I perceive it to be today, that all the things that we are talking about at this kindling conference are exactly the same kind of issues that we deal with in any epilepsy or synaptic plasticity meeting, that they are in fact a set of overlapping problems that we need to deal with and kindling is a way, a technical way, of approaching that kind of question? [ABSTRACT FROM AUTHOR]

When Graham Goddard and colleagues were performing experiments in 1968 that led to the observation of kindling, there was only limited appreciation that neurons and neural circuits were capable of the remarkable capacity for adaptation, alteration, and reorganization of function now referred to as "plasticity". At the time of Goddard's experiments,1,2 the adult brain was still generally regarded as "hard-wired". In the developing brain, neural activity was recognized to influence synapse formation and patterning of neural connections, but the potent effects of neural activity on neurons and circuitry throughout the lifespan, now appreciated as fundamental processes of neurobiology, were not recognized. [ABSTRACT FROM AUTHOR]

Determining the circuitry of a seizure has been of interest for many years. The primary goals have been to define the regions that are involved in the seizures and to determine the roles that these different regions play in the course of a seizure. Kindling has been used over the years to examine this issue, and it has many advantages for this purpose. Some of the advantages include the ability to determine exactly where to stimulate, when to stimulate and to time the stimulation so that potentially modifying treatments can be given at predetermined points around the seizure inducing stimulation. Over the years a number of observations have been made regarding the potential roles of the different regions of the brain based on seizure thresholds, speed of kindling, ability to alter established seizure patterns or to slow the rate of kindling.9, 15, 16, 22 These observations have been interpreted in terms of presumed or known anatomical connections, and our understanding of the significance of findings has evolved with our improving understanding of the anatomical relationships among the different regions. In this paper we will re-examine the issue of seizure circuitry through a series of experiments that were designed around past observations and evolving information about neural networks in the limbic system. [ABSTRACT FROM AUTHOR]

The tendency for chemical, mechanical, electrical, biological and artificial neural network systems to undergo oscillatory behaviour has been extensively studied. At least two general principles appear to emerge from these studies. Systems have a greater tendency to oscillate if they become more strongly interconnected and simpler. We have chosen to investigate whether these two principles apply to seizure phenomenon within the vertebrate brain. We postulate that during progression to a more seizure prone state, the involved neuronal system will become more strongly interconnected and simpler. This chapter contains a series of observations from the synaptic and cellular levels in the neocortex of rats that support this postulate. Furthermore, the consequence of greater synaptic efficacy of excitatory connections is manifested at the systems level as a series of predictable changes in network behaviour. We present an overview of a variety of studies that we have conducted in the neocortex of rats and cats that examined evoked and spontaneous network properties. We argue that the networks show greater interconnection and reduced functional specificity as a consequence of kindling-induced alterations. [ABSTRACT FROM AUTHOR]

Characterizing the differences in kindling rates and associated convulsive behaviors following kindling of various structures may aid in understanding the structural and functional mechanisms of epileptogenesis. Overall, the structures and pathways that are critical to kindling are largely unknown. The results of recent research suggest a role for the CLA, namely that the CLA may be part of a network of structures involved in seizure generalization. The anterior CLA is highly susceptible to kindling, involving a pattern of dual-phase seizure development.1 [ABSTRACT FROM AUTHOR]

The granule cells (GC) of the dentate gyrus (DG) are very exciting cells, although it seems that they can also be very inhibiting cells. They contain and release the excitatory amino acid glutamate, the metal Zn++, the peptides Y, and dynorphin, brain derived neurotrophic factor (BDNF), and it has recently been well established that they also have the necessary machinery to synthesize, vesiculate and release the inhibitory amino acid GABA.6, 12 Among all these chemical messengers, glutamate is the only one with fast-acting excitatory actions. There is no doubt on the excitatory nature of the GC, but when they fire at high frequencies, peptides Y14 and dynorphin35 are released to produce inhibition and glutamate reaches an extracellular concentration that, by spilling over, activates presynaptic mGlu and kainate receptors21, 28 to inhibit further release. To complicate things further, GABA can be released from the mossy fibers (MF) under certain conditions. [ABSTRACT FROM AUTHOR]

Experimental studies suggest that the brainstem, particularly the brainstem reticular formation (RF), is involved in the secondary generalization of partial seizures originating in the forebrain. Electrolytic lesioning of the midbrain involving the medial part of the mesencephalic RF (MRF) prior to amygdala (AM) kindling retards the development of AM kindling.10 Extensive midline bisection of the brainstem (the midbrain to the pons) can inhibit the development of a stage 5 AM kindled seizure.8 In feline AM kindling, the emergence of afterdischarge (AD) in the ipsilateral and then contralateral midbrain reticular formation precedes generalization and synchronization of AD leading to the final stage 6 generalized convulsion.45 In addition, a unilateral lesion (ipsilateral to the kindled AM) in the midbrain reticular formation not only elevates the established generalized seizure triggering threshold but also prevents recalling the kindled stage 6 seizures in cats.45, 47 However, bisection of the forebrain commissures does not prevent stage 6 convulsive development.46 In prefrontal kindling in epileptic Senegalese baboons, Papio papio, bisynchronous electroencephalographic discharges in the bulbar RF are associated with photically induced generalized convulsions and AM kindled generalized seizures.44 [ABSTRACT FROM AUTHOR]

The entorhinal cortex is the main input and output region for the hippocampus. Perirhinal and postrhinal cells send their axons into superficial layers of the EC where they interact with projection cells in layer II and III of the entorhinal cortex but also with apical dendrites of the deep layer entorhinal cortex cells.1 These receive input from olfactory cortex and subiculum and cholinergic input from the basal ganglia and the nucleus basalis Meynert as well as from the septum. Layer II stellate cells form the major portion of the perforant path, which projects to the dentate gyrus, while layer III cells project to the subiculum and in addition to the stratum moleculare of the CA1 area and perhaps also to area CA3.2 Studies on the normal interaction between the entorhinal cortex and hippocampus from adult rats have revealed that seizure susceptibility is larger in the EC than in the hippocampus, which tends to develop only interictal discharges and short ictal events.3,4 In adult rats seizure like events spread from the EC to the subiculum, but rarely fully recruit area CA1 and the DG. This limitation of spread seems to relate to the extensive feedforward and feedback inhibitory network in the DG and the prominent activation of inhibitory interneurons in area CA1.5 The DG was therefore assumed to play a gating role in transfer of information from layer II of the EC to the DG.6 We asked the question whether the properties of EC layer II stellate cells also contribute to the limitation of seizure spread from the EC through the DG to area CA3. Indeed layer II stellate cells express a flat input output curve when stimulated at low frequencies. [ABSTRACT FROM AUTHOR]

Inhibition is mediated by two main types of GABA receptors — ionotropic GABAA receptors that directly open Cl− channels, and metabotropic GABAB receptors that act through G-protein coupled second messenger systems.1, 2, 3 Postsynaptic GABAB receptors are found mainly on the dendrites of pyramidal cells (Fig. 1) and interneurons in the hippocampus, and they induce a slow K+-mediated inhibitory postsynaptic current (IPSC).2 Presynaptic GABAB receptors at the axon terminals (Fig. 1) mediate presynaptic inhibition of GABAergic terminals (autoreceptors) or glutamatergic terminals (heteroreceptors), likely by decreasing Ca2+ influx.2, 4 [ABSTRACT FROM AUTHOR]

The voltage dependent sodium current determines the upstroke of the action potential, and it is therefore one of the determinant factors for neuronal excitability. The steep voltage dependence of activation as well as inactivation in combination with its fast kinetics imply that even relatively small changes in sodium current properties will have a significant influence on, for example, cell firing frequency. It is therefore not surprising that the majority of antiepileptic drugs (AEDs) exert their action by modulating sodium current properties that are relevant for cell firing.1 The aim of this study is to parameterize the sodium current in CA1 hippocampal pyramidal cells using the classical description originally provided by Hodgkin and Huxley2, 3 employing voltage clamp data obtained from neurons acutely isolated from the rat hippocampus. Such a description does not comprise every possible detail of the present knowledge of the sodium channel. Nevertheless it appears to be sufficient to describe the changes observed in the inactivation function of the sodium current in neurons isolated from the epileptic focus in rats that were either kindled4 or in which a status epilepticus model was generated.5 [ABSTRACT FROM AUTHOR]

The electrically and chemically induced kindling is a model of human epilepsy. Whereas the electrical kindling is regarded as a model of complex partial epilepsy,1,2,3 the chemical kindling6,7 is a model of primary generalized epilepsy.5 Although pentylenetetrazol (PTZ) kindling has often been used to explore the mechanisms of seizure genesis and neurobehavioral and neurophysiological consequences of seizures, limited attention was paid to the contribution of this model in the mechanisms of the generalized nonconvulsive epilepsy-absence model.8-17 Meanwhile, complex evaluation of this model should be performed as far as divergent and even opposite mechanisms of epileptogenesis might be suspected in the course of generalized absence and convulsive stages of PTZ-kindling. Thus, first one is characterized by absence-like manifestations (spike-wave discharges (SWD)-bursts) and is supported by hyperexcitable state of all cortical neurons, including inhibitory ones, while receptors of GABA are preserved and their hyperactivation is resulted in typical generalized spike-wave generation.18-19 Further increasing of epileptogenic stimuli is followed by collapse of GABA control, and precipitation of generalized seizures as a result. [ABSTRACT FROM AUTHOR]

Neural mechanisms underlying convulsive events are believed to be distinctly different from those of absence seizures.1 Typical absence epilepsy has been suggested to be related to a predominance of inhibitory activity, in contrast to generalized or focal convulsive seizures where an excess of excitatory activity is present.2 Likewise, drugs that exacerbate seizure activity, clinically and in animal models, support the hypothesis concerning distinct differences between convulsive and non-convulsive epileptic events. It has long been known that carbamazepine, oxcarbazepine and phenytoin are successfully used in the treatment of partial and secondary generalized seizures, whereas typical absence seizures are clearly exacerbated by carbamazepine and phenytoin.3, 4 Similarly, despite the fact that vigabatrin is a highly effective anticonvulsive agent against partial seizures,5 two patients with idiopathic generalized absence epilepsy in whom vigabatrin increased the frequency and severity of absence and absence status were reported by Panayiotopoulos et al.6 On the other hand, absence seizures in both animal models and humans respond to ethosuximide and trimethadion, which are ineffective against partial seizures.3, 7 Models of convulsive events as well as non-convulsive seizures offer several unique opportunities to understand the pathophysiology of epileptogenesis in animals and perhaps, by extrapolation, in humans. [ABSTRACT FROM AUTHOR]

Febrile convulsions are a common form of childhood seizure, occurring in approximately 2-5 % of infants and young children.1 Simple febrile convulsions are the most common, defined as a generalized seizure of short duration (<15 minutes) that occurs during a febrile illness,2, 3 in a child between the ages of 6 months to 6 years. The significance of simple febrile convulsions is debated, with many considering them to be benign, as they do not result in gross neuropathology4 nor do they increase the risk of partial-complex epilepsy (e.g., 5 2, 6) or cognitive impairments.7-9 Conversely, some researchers have observed that in adulthood, individuals who have experienced simple febrile convulsions have a slightly higher risk of partial-complex epilepsy in later life (e.g., 3, l0) and may exhibit cognitive deficits, including: decreased ability to sustain attention; deficits in some types of learning and non-verbal memory; delayed recognition; and decreased visuomotor skills (e.g., 1, 11). As such, the question of whether febrile convulsions enhance susceptibility to seizure disorders, cognitive impairments or other pathologies remains unresolved. [ABSTRACT FROM AUTHOR]

Several epileptic syndromes have a genetic background. Thus, genetic models of epilepsy in rodents provide a useful tool to study basic mechanisms of seizures.1 Using selective breeding technique, two new strains of rats with differential rates of amygdala kindling were produced and named "FAST" and "SLOW" kindling rats.2, 3 Although the FAST and SLOW kindling rats have differences in kindling paradigms in several brain regions such as hippocampus, piriform and perirhinal cortices, the most striking differences were found during amygdala kindling. Besides the faster kindling rate, amygdala stimulation in FAST rats resulted in significantly longer afterdischarges (ADs) both prior to and after the kindling compared to the SLOW rats.2, 3 The differences in the excitability of these two strains were determined in adult rats. [ABSTRACT FROM AUTHOR]

Administration of corticosteroids is common in obstetrics. Corticosteroids are frequently used in pregnant women between 24-34 gestation weeks, if there is a danger of imminent delivery with subsequent respiratory distress syndrome of the newborn.1 In this situation, one course of corticosteroid therapy is applied, usually consisting of 2-4 injections of betamethasone or dexamethasone spread over 24-48 hours. Follow-up studies in humans have demonstrated that this therapy regimen significantly improves the chance of the premature newborn for survival with no long-term side effects. [ABSTRACT FROM AUTHOR]

In 1990, we published the first report of amygdala kindling in kittens and the first description of a spontaneous seizure model in immature animals.3 We found that spontaneous epilepsy was more likely to occur after amygdala kindling in preadolescents than in adults and that the post-kindling onset was most rapid in the youngest animals. This update is intended to fill some gaps in the initial report on the ontogeny of temporal lobe epilepsy.4 [ABSTRACT FROM AUTHOR]