Ttv Latent Period
FIGURE 3 A Ictal-like discharges recorded in low Ca2+ o in the CA1 region. Traces are shown at different time scales (expanded time frame in middle trace, slower time frame below). (Adapted from Konnerth et al., 1986.) B Spontaneous epileptiform discharges recorded in Mg2+-free artificial cerebrospinal fluid (aCSF). These discharges were modulated by application of the N-methyl-D-aspartate (NMDA) receptor antagonist APV. (Adapted from Mody et al., 1987.) C Spontaneous ictal-like discharge...
Characteristic Features
Behavioral and Electrographic Features Flathead Mutant Rat In the first postnatal week, flathead pups display severe generalized seizures and motor deficits. During ambulation, astatic episodes can be observed and are characterized by the splaying of limbs. Mutant rats also often fall to one side during walking but are able to right themselves quickly. The falling and astatic episodes in flathead mutants are likely related to general muscle weakness, since flathead mutants cannot grip a small...
Sensorimotor Cortex Model
The advantages of the alumina gel model of cortical focal epilepsy are several. First, it is a model that is focal in its initiation and then proceeds with time to produce spontaneous focal seizures that often become generalized. Focal motor seizures in the human are well characterized, and this model produces seizures that are extremely similar to those in regard to their behavior, electrophysiology, biochemistry, neuropathological, and pharmacologic responses (Lockard, 1980). The second...
Modeling to Test New Therapies
Beginning with studies of phenytoin, investigations in animal models have been used to determine the efficacy and safety of new antiepileptic compounds before they are tried in patients. Animal models of epileptic seizures have been indispensable for this purpose. With one exception (leve-tiracetam), however, all potential new antiepileptic compounds have been screened against only two mouse models of epileptic seizures maximal electroshock and subcutaneous Metrazol (Levy et al., 2002)....
Methods Of Preparation And Generation Of Epileptiform Discharges
The methods used to isolate and maintain in vitro a guinea pig brain have been extensively described (de Curtis et al., 1991, 1998 Llinas et al., 1981, 1989 Muhlethaler et al., 1993). Young adult guinea pigs weighing 150 to 250g are anesthetized with 70mg kg tiopenthal, administered intraperioneally. A study of the time course of barbiturate washout in this preparation demonstrated that within 1 hour from the in vitro isolation, the brain concentration of the anesthetic measured by...
Alumina Gel Injection Models of Epilepsy in Monkeys
SHAPIRO, LASZLO SERESS, AND ROY A. BAKAY Epilepsy is a neurologic disorder that has been modeled in many animals, including the monkey. This chapter deals with two types of alumina gel injections that model two different human epileptic disorders. Where alumina gel is injected into the brain determines what type of epilepsy it models. For example, alumina gel injections into sensori-motor cortical regions produce seizures that have been used as a model for posttraumatic...
In Vitro Models Of Absence Epilepsy
The Ferret Dorsal Lateral Geniculate Nucleus Slice A Model for the Transformation of Spindle Waves into Spike-Wave Discharges A number of thalamic in vitro models have been developed to investigate the mechanisms underlying the generation and spread of spike wave (SW)-like discharges in this brain structure. The ferret primary visual thalamic relay nucleus (dorsal part of the lateral geniculate nucleus, LGNd) and the associated section in the RT nucleus (termed the perigeniculate nucleus, PGN)...
Consequences of Brain Injury
Head trauma and brain injury are significant factors in the etiology of some epilepsies, but the underlying mechanisms have received little attention. The percentage of all victims of a serious head injury that go on to develop posttraumatic epilepsy has been estimated at 10 to 34 , depending on the severity of the injury. One of the strongest predictors of the likelihood of posttraumatic epilepsy is a penetration of the dura (Willmore, 1990). A striking characteristic of post-traumatic...
Relevance Of Alcohol Withdrawal Seizures In Rodents To The Human Condition
Although alcohol withdrawal seizures in rodents do not represent a perfect model of human alcohol withdrawal seizures, the available evidence indicates that the animal models are valid in many respects. As noted, most alcohol withdrawal seizures in humans are generalized tonic-clonic seizures. Similarly, the various forms of alcohol withdrawal seizures in rodents represent generalized convulsions. In both humans and rodents, the peak incidence of alcohol withdrawal related generalized seizures...
Testing Pharmacological Agents In Animal Models Of Alcohol Withdrawal Seizures
Because alcohol withdrawal-related AGS and HIC can be elicited at the will of the experimenter during a defined period after cessation of alcohol intake, the anticonvulsant properties of pharmacologic agents can be easily studied (unlike the situation with spontaneous seizure models, where seizures occur unpredictably, requiring sophisticated monitoring systems and less robust trial designs). A limitation of these models is that AGS or HIC do not occur in every animal. However, the incidence...
Metabolic Changes Following Alcohol Withdrawal
Alcohol intoxication decreases local cerebral glucose utilization (LCGU) in many areas of the brain, including the limbic system, cerebellum, and motor system (Eckardt et al., 1992). The most striking effects on LCGU are observed in the IC (Grunwald et al., 1993), in accordance with other evidence indicating that this brain site is a major target of alcohol. Alcohol withdrawal is associated with increased brain glucose uptake, oxygen consumption, and blood flow (Eckardt et al., 1992 Hemmingsen...
Singleneuron Firing During Cellular Electrophysiology Of Alcohol Withdrawal Seizures
During alcohol withdrawal-related AGS, the cortical electroencephalogram typically shows no sign of paroxysmal activity compatible with the idea that the seizures are mediated largely in the brainstem (Hunter et al., 1973 Maxson and Sze, 1976). Nevertheless, epileptiform activity has been observed in the hippocampus, but with a significant delay after the onset of AGS, suggesting a role in the propagation rather than in the initial generation of the seizures (Hunter et al., 1973). Acute alcohol...
Alcohol Withdrawal Seizures
ROGAWSKI Ethyl alcohol (ethanol) is a central nervous system (CNS) depressant that exerts diverse behavioral actions. At low blood concentrations, alcohol produces euphoria and behavioral excitation, and at concentrations greater than 0.08 g dl (17 mM), it significantly impairs motor skills. Concentrations of 0.15 to 0.30 g dl induce acute intoxication, which manifests as drowsiness, ataxia, slurred speech, stupor, and coma. The acute effects of alcohol on brain...
Summary And Conclusions
The major advantage of the epileptic Papio and GEPRs models is their clearly defined predisposition to convulsive epilepsies and the heritable nature of this predisposition. As in patients with idiopathic generalized epilepsy, the disorder in these genetic models is multigenic rather than monogenic. The epileptic P. papio is a good model of idiopathic secondarily generalized focal seizures that are triggered by flickering light. These mammals appear to have a reduced seizure threshold in both...
Studying Epilepsy Using The Slice Preparation
Many different types of epilepsy exist. Hence multiple models have been developed, for example, partial or generalized epilepsies and convulsive or nonconvulsive epilepsies. A similar diversity of models has been reported using the hippocampal slice preparation (and variations thereon), most focusing on generating activity relevant to TLE. Many different issues can be addressed in the slice preparation. A major area of investigation has been the issue of ictogene-sis, including where ictal...
Modeling to Devise New Approaches for Diagnosis
The first laboratory test capable of measuring human cerebral function was the electroencephalogram (EEG), which rapidly became the premier diagnostic tool for epilepsy and provided a key element for the classification of epileptic seizures (Commission on Classification, 1981). Interictal and ictal epileptiform discharges on EEG are not only useful for making a general diagnosis of epilepsy, but they also provide a basis for determining what type of epilepsy is present and for localizing the...
Pavel Mares And Hana Kubova
Seizures induced by electrical stimulation exhibit one advantage The epileptogenic agent is acting only during application of current and epileptic activity is no longer contaminated by this agent. On the other hand, electrical current stimulates all neuronal and nonneuronal elements in the stimulated nervous tissue. Electrically induced seizures may be divided according to the mode of stimulation into two main types (1) those elicited by stimulation of the whole brain (electroshock seizures)...
Temporal Lobe Model
Alumina gel injections into the temporal lobe of rhesus monkeys were used in an attempt to mimic complex partial seizures associated with temporal lobe epilepsy in humans (Ribak et al., 1998). Our analysis is based on injections of alumina gel into several regions of the temporal lobe in rhesus monkeys. Thus structures that were injected include the hippocampus, entorhinal and perirhinal cortices, and the amygdala. In all cases, complex partial and secondarily generalized seizures were...
Info
FIGURE 2 The two types of seizures in the Wistar Albino Glaxo Rijswijk strain WAG Rij of rat. The first is a type II SWD, which is followed by a type I SWD similar to that shown in Figure 1 . The trace shows a differential elec-troencephalographic EEG recording with two active EEG electrodes, one at the frontal and one at the parietal cortex courtesy of Ulrich Schridde . FIGURE 2 The two types of seizures in the Wistar Albino Glaxo Rijswijk strain WAG Rij of rat. The first is a type II SWD,...
Conclusion
Acute seizures can be induced by administration of chemoconvulsant drugs via different delivery routes sub-Q, IP, IV, ICV, or inhalation . Main categories of convulsant drugs used for the production of acute seizures affect the inhibitory GABA or glycine transmission, affect excitatory amino acid transmission, or act on ACh receptors. The seizures are primarily or secondarily generalized, and some of their behavioral, EEG, metabolic, and neuropathologic features are age specific. An additional...
Introduction
Mongolian gerbils Meriones unguiculatus are a member of the rodent family Muridae. They reach puberty at 65-85 days old, weigh 70-110g as adults, and live for approximately 3 years Cheal, 1987b . They are native to desert regions of Mongolia and northeastern China, where they burrow extensively and live on grain, seeds, roots, and grass. Their head is adapted for burrowing, being shorter and broader than that of rats. Gerbils live in large social groups and are extremely territorial, earning...
Scott C Baraban
Pediatric epilepsy models are confined primarily to rodents. Although using a rodent model of a human neurologic disorder has distinct advantages, there is no rationale to support our almost exclusive reliance on this species. Indeed research questions related to genetic modifiers of pediatric epilepsy syndromes, high-throughput anticonvul-sant drug screening, and rapid genetic manipulations aimed at analysis of basic cellular mechanisms of epilepto-genesis could be better suited to a simple...
Insights Into Human Disorders
Underlying Mechanisms Primary Generalized Epilepsies In both rodent and feline models of absence seizures, the evidence suggests that the mechanisms that underlie the SWD bursts that characterize this seizure type may be related to the thalamocortical mechanism that mediates spindles and recruiting responses Crunelli and Leresche, 2002 . Seizures with SWD complexes preferentially evolve from sleep oscillations. They are initiated in the neocortex and spread to the thalamus after a few seconds...
Caas Craas
AY-9944, AY BCC, bicuculline CAAS, chronic atypical absence seizures CRAAS, chronic refractory atypical absence seizures EEG, electroencephalography GAERS, Genetic Absence Epilepsy in Rats from Strasbourg GBL, gamma butyrolactone GHB, gamma-hydroxybutyrate HD, high dose LD, low dose MAM, methylazoxymethanol acetate PCL, penicillin PTZ, pentylenetetrazole SD, Sprague-Dawley TAS, typical absence seizures VEEG, video electroencephalography W, Wistar. a 600.000 units per kilogram. to 7 seconds. The...
Pathophysiologic Mechanisms Of Childhood Absence Epilepsy
Clinical evidence indicates that absence seizures are associated with states of decreased vigilance, such as drowsiness Crunelli and Leresche, 2002 . In an early model of generalized epilepsy that used systemic or focal cortical application of penicillin penicillin-generalized epilepsy model for review, see Gloor and Fariello, 1988 , investigators observed that SWDs on the EEG e.g., Figure 1A developed gradually from sleep spindles during early stages of slow-wave sleep Kostopoulos et al., 1981...
Christophe Bernard
INTRODUCTION DESCRIPTION OF THE HIPPOCAMPAL SLICE PREPARATION General Features of Acute Slice Preparations The development of the brain slice preparation by Yamamoto and McIlwain Yamamoto and McIlwain, 1966 allowed major breakthroughs in the understanding of basic neurobiological processes. All fields of neuroscience benefited from this development, including anatomy, physiology, pharmacology, molecular biology, biochemistry, biophysics, and computer modeling. Brain slices, usually thin...
Seizures In Gerbils
The incidence of epilepsy in gerbils from randomly bred colonies and commercial vendors varies between 3 and 98 Theissen et al., 1968 Harriman, 1988 Cutler and MacKintosh, 1989 Bertorelli et al., 1995 . This wide range in seizure incidence may be attributable to genetic differences between colonies or to differences in seizure testing methods. For example, with repeated testing over months, 100 of a large, outbred group of gerbils displayed at least one seizure Scotti et al., 1998 . Some...
General Conclusions
During the last 20 years, the GAERS and the WAG Rij strains of Wistar rats have proven to be valid and predictive models of human absence epilepsy. Although some features of this form of epilepsy appear species specific e.g., frequency, ontogeny, and aging , the pharmacologic reactivity and the underlying circuits described in both strains appear very similar to the human pathology. Differences between the two strains and recent identification of QTLs suggest that several genetic mechanisms can...
Epileptic Seizures
The ILAE classified epileptic seizures most recently in 1981 Commission on Classification, 1981 Table 1 , and this classification is undergoing revision Engel, 2001 . The 1981 classification is based solely on clinical and EEG descriptive phenomena. It defines seizures that begin in a part of one hemisphere as partial seizures and those that begin in both hemispheres at the same time as generalized seizures. Generalized seizures are often divided into TABLE 1 International Classification of...
Acute Slices
There are multiple variations of preparation techniques for acute slices. The precise method should depend on the purpose of the study and the area of interest. Initially most laboratories used a tissue chopper for cutting the tissue into thin slices later, vibratomes were adopted in many laboratories because they appeared to make slices with less mechanical damage. Efforts have been made to determine which cutting parameters with the vibratome are most important for preservation of fine tissue...
References
Veratridine-enhanced persistent sodium current induces bursting in CA1 pyramidal neurons. Neuroscience 71 625-632. Andersen, P. 1975. Organization of hippocampal neurons and their interconnections. In The Hippocampus. Eds. R.L. Isaacson and K.H. Pribram. pp. 155-175. New York Plenum Press. Anderson, W.W., Lewis, D.V., Swartzwelder, H.S., and Wilson, W.A. 1986. Magnesium-free medium activates seizure-like events in the rat hip-pocampal slice. Brain Res 398...
Thalamic Thalamocortical and Corticocortical Models of Epilepsy with an Emphasis on Absence Seizures
THOMAS BUDDE, HANS-CHRISTIAN PAPE, SANJAY S. KUMAR, AND JOHN R. HUGUENARD Absence epilepsy is an idiopathic, generalized, and non-convulsive form of epilepsy with an as yet unknown polygenic background for review, see Crunelli and Leresche, 2002 . A typical absence episode consists of a sudden epileptic seizure with severe impairment of consciousness. Although the interictal electroencephalogram EEG appears normal, the ictal EEG is characterized by phases of bilateral, synchronous 2.5- to...
Advantages of the Acutely Dissociated Cell Preparation
A critical feature of the acutely dissociated cell is that action potential electrogenesis is preserved. The action potential is not only a sensitive indicator of channel activity, but it is also the output mechanism of the neuron. Most studies of the acutely dissociated cell aim toward understanding the roles of ion channels in action potential generation and patterning. One of the most significant advantages of the acutely dissociated cell preparation is that different stages of neuron...
The Genetically Epilepsyprone
Clinical Applicability Characteristics and Background Two independently derived inbred strains of genetically epilepsy-prone rats GEPRs have been developed the moderately epileptic GEPR-3 and the more severely epileptic GEPR-9. Details for the development of the GEPR-3 and GEPR-9 strains have been previously described Reigel et al., 1986 . The GEPR strains have been developed via inbreeding of naturally occurring epilepsy occasionally seen in Sprague-Dawley rats. At this point in the...
In Vitro Isolated Guinea Pig Brain
MARCO DE CURTIS, LAURA LIBRIZZI, AND LAURA UVA The isolated guinea pig brain preparation maintained in vitro by arterial perfusion has been utilized to develop a model of acute epileptogenesis in the temporal lobe. The technique is ideal for performing high-resolution electro-physiologic and optical imaging studies of the generation and the propagation patterns of interictal and ictal epilepti-form discharges induced by different acute pharmacologic treatments in vitro. The preparation...
J
FIGURE 3 Rhythmic, spindle-shaped discharges induced by a low systemic dose of pentylenetetrazol PTZ in a Wistar rat. These discharges with a crescendo-decrescendo pattern were associated with freezing behavior motionless stare . Electrocorticograms from RF, right frontal sensorimo-tor cortex RO, right occipital visual cortex LF, left frontal cortex LO, left occipital cortex. zures. Twitches and tonic-clonic seizures are recorded throughout development. However, there is limited occurrence of...
Characteristic Of The Activity Generated By Human Epileptic Neurons
One important topic in studying human epileptic tissue is whether spontaneous epileptiform network activity is maintained in vitro after tissue excision. Field potential recordings have demonstrated network synchronization as reflected in population spikes Figure 2 . These spontaneous discharges, which resemble epileptiform spikes seen with FIGURE 2 Spontaneous field potential discharges and associated intracellular responses in human neocortical A and subicular B tissue in vitro are sensitive...
B
Combined thalamocortical slices 550-650 mm , involving a hybrid coronal plane forming a 45-degree angle with the sagittal plane, can be obtained on a vibratome Figure 4 . Typically two slices are obtained from each hemisphere at the level of the VB. After cutting, slices are transferred to an interface tissue chamber perfused with ACSF 32-35 C . Extracellular field potentials are recorded with ACSF-filled electrodes 2-8MW positioned under visual control in cortex and thalamus...
Phillip C Jobe And Ronald A Browning
Some people with epilepsy are known to have seizures induced by flickering light, thinking, music, contemplation of a tune, reading, and eating. Similarly, some animals exhibit seizures in response to conditions that do not cause seizures in normal mammals-conditions such as sound, flickering light, proprioception, touch, postural changes and emotional factors Buchhalter, 1993 Jobe et al., 1991 King and LaMotte, 1989 Loscher, 1984 Seyfried et al., 1986 Suzuki and Nakamoto, 1977 . By selectively...
Epilepsies and Epilepsy Syndromes
The current ILAE classification of epilepsies and epilepsy syndromes Table 3 was approved in 1989 Commission on Classification, 1989 and is also now undergoing revision Engel, 2001 . The 1989 classification divides epilepsies into generalized and localization-related categories, depending on whether the characteristic seizures begin simultaneously on both sides of the brain or in a part of one hemisphere. Generalized epilepsies are never associated with partial seizures, but...
Models of Chemically Induced Acute Seizures
This chapter reviews models of generalized seizures induced by systemic administration or focal application of chemical agents. For some substances, there is an unavoidable overlap with the preceding chapter on absence models or with subsequent chapters on exploring status epilepticus SE or the effects of repeated seizures. This chapter intends to help the investigator develop and use a particular model. Chemical agents are organized by the route of administration and then by the prevailing...
The Use of Brain Slice Cultures for the Study of Epilepsy
THOMPSON, XIANG CAI, CELINE DINOCOURT, AND MICHAEL W. NESTOR Organotypic brain slices are becoming increasingly useful and advantageous for a variety of neurobiological questions, including the study of epilepsy. In this chapter, we provide a brief review of some of the defining characteristics of this technique. We also review some recent studies in which these cultures have been used to examine various issues pertaining to the causes and consequences of epilepsy to illustrate the...
Contributing Authors
Massimo Avoli, Department of Neurology and Neurosurgery, McGill University, Montreal, Canada Roy A. Bakay, Department of Neurological Surgery, Chicago Institute of Neurosurgery and Neuroresearch, Rush Presbyterian-St. Luke's Medical Center, Chicago, IL Scott C. Baraban, Department of Neurological Surgery, University of California San Francisco, San Francisco, CA Tallie Z. Baram, Departments of Pediatrics and Anatomy and Neurobiology, University of California Irvine, Irvine, CA Stefania...
Methods For Induction Of Alcohol Dependence And For Monitoring Withdrawal Seizures
Species, Strain, Gender, and Age Considerations As in humans, an alcohol withdrawal syndrome that includes generalized tonic-clonic seizures has been observed in the mouse, rat, cat, dog, monkey, and chimpanzee Ellis and Pick, 1970 Essig et al., 1969 Freund, 1969 Guerrero-Figueroa et al., 1970 Majchrowicz, 1975 Pieper et al., 1972 . In all species, the signs of alcohol withdrawal last for 1 to 3 days, after which behavior returns to normal and there is no enhanced seizure susceptibility....
Advantages And Limitations Of The Zebrafish Model
The application of our larval zebrafish model to epilepsy research is probably limited only by one's imagination. As discussed in the previous section, a simple application of this model would be to evaluate drugs useful in generalized epilepsy syndromes. One might also consider forward- and FIGURE 4 Response to antiepileptic drugs. a Representative tectal field recordings obtained from a zebrafish bathed in normal Ringer's medium plus 15 mM pentylenetetrazol PTZ baseline and 45 minutes after...
Conclusions
Foremost, the potential usefulness of a zebrafish model of pediatric epilepsy should be evaluated with respect to the type of problem to be solved. In the preceding sections, I have tried to provide examples of the features of this model that are clinically relevant. These features include distinct stages of seizure behavior, evidence of abnormal electrical discharge in a CNS structure, seizure-induced expression of c-fos, and AED sensitivity. There are many more features of this model that...
Neuropathological Effects Of Alcohol Withdrawal
In humans, alcohol withdrawal seizures have been associated with ventricular and sulcal enlargement as well as significantly smaller volume of temporal lobe white matter and hippocampal sclerosis Essardas-Daryanani et al., 1994 . In animal models, there is evidence that alcohol intoxication can lead to selective damage to specific brain regions, including the hippocampus Ikonomidou et al., 2000 Walker et al., 1980 . Withdrawal from long-term alcohol consumption can aggravate alcohol-induced...
Specific Culture Methods
CNS neurons can be cultured in a variety of formats, depending on the desired experimental paradigm. For most physiologic experiments, neurons are cocultured with glial cells in a relatively enriched medium Dichter, 1978 . For other experiments neurons can be grown in an almost glial-free environment with carefully controlled and characterized media Brewer, 1995 Brewer et al., 1993 Evans et al., 1998 . Cells can be grown at varying densities, depending on the nature of the experiment to be...
Epileptiform Activity In Organotypic Slice Cultures
Potentially the best suited preparations for studies on seizure generation and seizure-induced cell death are organ-otypic slice cultures. Organotypic cultures maintain some of the intrinsic properties of the tissue, including the most important aspects of connectivity. However, the preparations are usually made from pups P6-P10 and then studied after 7 to 30 days in vitro therefore these preparations do not necessarily represent adult tissue. The preparations are usually maintained in an...
