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Article: Animal models used in the screening of antiepileptic drugs.

Kupferberg, H

2001 Volume 42 Suppl 4, Page(s) 7–12

Abstract: ... the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used ... response. No single model can be used to identify potential compounds adequately for development. The full ... to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism ...

Abstract	The identification of potential therapeutic agents for the treatment of epilepsy requires the use of seizure models. These models can be either in vivo or in vitro, mechanism specific, mechanism independent, or seizure specific. To be predictive of therapeutic activity in patients, the models should approximate the events that precipitate seizures in humans. Model validation is defined by determining the pharmacologic characteristics using known clinically effective drugs. Mechanism-independent models were used to identify the first antiepileptic drugs [AEDs; e.g., phenobarbital (PB) and phenytoin (PHT)]. Mechanism-specific models are based on the fundamental process by which seizure propagation and inhibition occurs. Seizure-type models identify a compound's potential based on its effects on electrographic and behavioral response. No single model can be used to identify potential compounds adequately for development. The full pharmacologic-anticonvulsant profile of a potentially useful new therapeutic agent is required to ensure successful development.
MeSH term(s)	Acoustic Stimulation ; Amygdala/physiology ; Animals ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Anticonvulsants/toxicity ; Disease Models, Animal ; Drug Evaluation, Preclinical ; Electric Stimulation ; Electrodes, Implanted ; Epilepsy/drug therapy ; Epilepsy/etiology ; Epilepsy/physiopathology ; Gerbillinae ; Kindling, Neurologic/physiology ; Mice ; Mice, Inbred Strains ; Papio ; Pentylenetetrazole ; Rats ; Rats, Inbred Strains
Chemical Substances	Anticonvulsants ; Pentylenetetrazole (WM5Z385K7T)
Language	English
Publishing date	2001
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	216382-2
ISSN	1528-1167 ; 0013-9580
ISSN (online)	1528-1167
ISSN	0013-9580
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Zs.MO 475: Show issues

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Article ; Online: The anti-seizure potential of cysteine leukotriene receptor antagonists: A systematic review of animal studies.

Bano, Aysha / Garg, Aakriti / Mumtaz / Nidhi / Ashif Khan, Mohd

Epilepsy research

2024 Volume 200, Page(s) 107305

Abstract: ... the intensity of seizures in animal models of epilepsy.: Conclusion: In conclusion, CysLTR antagonists ... from working. They may be useful for treating epilepsy, especially for people who do not respond to other drugs ... Initially we identified 3823 studies. After screening using inclusion and exclusion criteria, 8 studies were ...

Abstract	Background: Emerging literature has suggested the antiepileptic activity of cysteine leukotriene receptor (CysLTR) antagonists in experimental animals of epilepsy. Leukotrienes are substances that cause inflammation and affect brain activity, blood flow, oxidation, and inflammation in the brain. These processes are related to epilepsy and its complications. CysLTR antagonists are drugs that prevent leukotrienes from working. They may be useful for treating epilepsy, especially for people who do not respond to other drugs. Therefore, the current study aims to systematically review the potential anti-seizure effect of CysLTR antagonists in experimental studies. Method: We systematically reviewed the online databases using online databases such as Google Scholar, science direct, and PubMed until December 2022 to identify experimental studies assessing the anti-seizure activity of CysLTR antagonists. The Systematic Review Centre for Laboratory Animal Experimentation (SYRCLE) was used to evaluate the risk of bias (RoB) of the included studies. Results: Initially we identified 3823 studies. After screening using inclusion and exclusion criteria, 8 studies were finally included in the current study. All included studies, reported that CysLTR antagonists reduced the intensity of seizures in animal models of epilepsy. Conclusion: In conclusion, CysLTR antagonists could be a potential therapeutic approach for the treatment of epilepsy. However, further preclinical and clinical studies are required to confirm their efficacy, safety, and mechanism of anti-seizure activity.
MeSH term(s)	Humans ; Animals ; Cysteine/therapeutic use ; Leukotriene Antagonists/pharmacology ; Leukotriene Antagonists/therapeutic use ; Epilepsy/drug therapy ; Epilepsy/complications ; Leukotrienes ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Inflammation
Chemical Substances	Cysteine (K848JZ4886) ; Leukotriene Antagonists ; Leukotrienes ; Anticonvulsants
Language	English
Publishing date	2024-01-20
Publishing country	Netherlands
Document type	Systematic Review ; Journal Article ; Review
ZDB-ID	632939-1
ISSN	1872-6844 ; 0920-1211
ISSN (online)	1872-6844
ISSN	0920-1211
DOI	10.1016/j.eplepsyres.2024.107305
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Zs.A 2193: Show issues

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Article ; Online: Cortical dysmorphology and reduced cortico-collicular projections in an animal model of autism spectrum disorder.

Kosmer, Kara / Kulesza, Randy

Cerebral cortex (New York, N.Y. : 1991)

2024 Volume 34, Issue 13, Page(s) 146–160

Abstract: ... and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening ... valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder ... to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed ...

Abstract	Autism spectrum disorder is a neurodevelopmental disability that includes sensory disturbances. Hearing is frequently affected and ranges from deafness to hypersensitivity. In utero exposure to the antiepileptic valproic acid is associated with increased risk of autism spectrum disorder in humans and timed valproic acid exposure is a biologically relevant and validated animal model of autism spectrum disorder. Valproic acid-exposed rats have fewer neurons in their auditory brainstem and thalamus, fewer calbindin-positive neurons, reduced ascending projections to the midbrain and thalamus, elevated thresholds, and delayed auditory brainstem responses. Additionally, in the auditory cortex, valproic acid exposure results in abnormal responses, decreased phase-locking, elevated thresholds, and abnormal tonotopic maps. We therefore hypothesized that in utero, valproic acid exposure would result in fewer neurons in auditory cortex, neuronal dysmorphology, fewer calbindin-positive neurons, and reduced connectivity. We approached this hypothesis using morphometric analyses, immunohistochemistry, and retrograde tract tracing. We found thinner cortical layers but no changes in the density of neurons, smaller pyramidal and non-pyramidal neurons in several regions, fewer neurons immunoreactive for calbindin-positive, and fewer cortical neurons projecting to the inferior colliculus. These results support the widespread impact of the auditory system in autism spectrum disorder and valproic acid-exposed animals and emphasize the utility of simple, noninvasive auditory screening for autism spectrum disorder.
MeSH term(s)	Animals ; Autism Spectrum Disorder/pathology ; Autism Spectrum Disorder/metabolism ; Autism Spectrum Disorder/chemically induced ; Disease Models, Animal ; Valproic Acid/toxicity ; Female ; Calbindins/metabolism ; Auditory Cortex/pathology ; Auditory Cortex/drug effects ; Auditory Cortex/metabolism ; Pregnancy ; Neurons/pathology ; Neurons/metabolism ; Rats ; Male ; Auditory Pathways/pathology ; Auditory Pathways/drug effects ; Prenatal Exposure Delayed Effects/pathology ; Rats, Sprague-Dawley ; Anticonvulsants
Chemical Substances	Valproic Acid (614OI1Z5WI) ; Calbindins ; Anticonvulsants
Language	English
Publishing date	2024-05-02
Publishing country	United States
Document type	Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
ZDB-ID	1077450-6
ISSN	1460-2199 ; 1047-3211
ISSN (online)	1460-2199
ISSN	1047-3211
DOI	10.1093/cercor/bhad501
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Article ; Online: Preclinical Animal Models for Dravet Syndrome

Aliesha Griffin / Kyla R. Hamling / SoonGweon Hong / Mana Anvar / Luke P. Lee / Scott C. Baraban

Frontiers in Pharmacology, Vol

Seizure Phenotypes, Comorbidities and Drug Screening

2018 Volume 9

Abstract: ... drug screening efforts using these models with a focus on assay protocols and predictive pharmacological profiles ... we will review the preclinical animal models for DS featuring inactivation of SCN1A (including zebrafish and mice ... these models respond to known AEDs. As such, we will also review the available literature and recent ...

Abstract	Epilepsy is a common chronic neurological disease affecting almost 3 million people in the United States and 50 million people worldwide. Despite availability of more than two dozen FDA-approved anti-epileptic drugs (AEDs), one-third of patients fail to receive adequate seizure control. Specifically, pediatric genetic epilepsies are often the most severe, debilitating and pharmaco-resistant forms of epilepsy. Epileptic syndromes share a common symptom of unprovoked seizures. While some epilepsies/forms of epilepsy are the result of acquired insults such as head trauma, febrile seizure, or viral infection, others have a genetic basis. The discovery of epilepsy associated genes suggests varied underlying pathologies and opens the door for development of new “personalized” treatment options for each genetic epilepsy. Among these, Dravet syndrome (DS) has received substantial attention for both the pre-clinical and early clinical development of novel therapeutics. Despite these advances, there is no FDA-approved treatment for DS. Over 80% of patients diagnosed with DS carry a de novo mutation within the voltage-gated sodium channel gene SCN1A and these patients suffer with drug resistant and life-threatening seizures. Here we will review the preclinical animal models for DS featuring inactivation of SCN1A (including zebrafish and mice) with an emphasis on seizure phenotypes and behavioral comorbidities. Because many drugs fail somewhere between initial preclinical discovery and clinical trials, it is equally important that we understand how these models respond to known AEDs. As such, we will also review the available literature and recent drug screening efforts using these models with a focus on assay protocols and predictive pharmacological profiles. Validation of these preclinical models is a critical step in our efforts to efficiently discover new therapies for these patients. The behavioral and electrophysiological drug screening assays in zebrafish will be discussed in detail including specific examples from ...
Keywords	epilepsy ; dravet syndrome ; drug discovery ; in vivo ; precision medicine ; antiepileptic drugs ; Therapeutics. Pharmacology ; RM1-950
Subject code	616
Language	English
Publishing date	2018-06-01T00:00:00Z
Publisher	Frontiers Media S.A.
Document type	Article ; Online
Database	BASE - Bielefeld Academic Search Engine (life sciences selection)

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Article: Animal models of drug-resistant epilepsy.

Potschka, Heidrun

Epileptic disorders : international epilepsy journal with videotape

2012 Volume 14, Issue 3, Page(s) 226–234

Abstract: ... differences. Non-responders to antiepileptic drugs have been described in the amygdala kindling model, as well ... antiepileptic drugs may serve as a translational model to provide a more clinical environment for drug ... testing. Drug resistance or a poor response to several antiepileptic drugs has been reported for the 6-Hz model ...

Abstract	Several animal models are discussed in order to outline features of difficult-to-treat or drug-resistant epilepsy. These models can be categorised as those which show a poor response to different antiepileptic drugs and those in which subgroups of drug-resistant animals are selected, based on interindividual differences. Non-responders to antiepileptic drugs have been described in the amygdala kindling model, as well as the chronic phase of post-status epilepticus models. Epileptic dogs which do not respond to standard antiepileptic drugs may serve as a translational model to provide a more clinical environment for drug testing. Drug resistance or a poor response to several antiepileptic drugs has been reported for the 6-Hz model, lamotrigine-pretreated kindled rats, pentylentetrazole-induced seizures in rats pre-exposed to pilocarpine, as well as following intrauterine exposure of rats to methylazoxymethanol. Using models to select non-responders is highly time-consuming and elaborate, limiting their use in routine drug-screening procedures. Current efforts to identify biomarkers of drug resistance may simplify the selection process, e.g. replacing several weeks of seizure monitoring by a single imaging scan. Moreover, further elucidation of mechanisms of resistance may help to design a series of ex vivo or in vitro screening procedures in order to evaluate whether a test compound is affected.
MeSH term(s)	Animals ; Anticonvulsants/therapeutic use ; Disease Models, Animal ; Drug Resistance ; Epilepsy/drug therapy ; Humans ; Kindling, Neurologic ; Models, Animal ; Status Epilepticus/drug therapy
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2012-09
Publishing country	France
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2086797-9
ISSN	1950-6945 ; 1294-9361
ISSN (online)	1950-6945
ISSN	1294-9361
DOI	10.1684/epd.2012.0532
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Zs.A 5740: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (2.OG) ab Jg. 2022: Lesesaal (EG)
Zs.MO 252: Show issues
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Article: Choosing the correct antiepileptic drugs: from animal studies to the clinic.

Holmes, Gregory L / Zhao, Qian

Pediatric neurology

2008 Volume 38, Issue 3, Page(s) 151–162

Abstract: ... rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be ... these age-related unique features, drugs used in children are generally the same as those in adults ... of gamma-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals (usually ...

Abstract	Epilepsy is a chronic condition caused by an imbalance of normal excitatory and inhibitory forces in the brain. Antiepileptic drug therapy is directed primarily toward reducing excitability through blockage of voltage-gated Na(+) or Ca(2+) channels, or increasing inhibition through enhancement of gamma-aminobutyric acid currents. Prior to clinical studies, putative antiepileptic drugs are screened in animals (usually rodents). Maximal electrical shock, pentylenetetrazol, and kindling are typically used as nonmechanistic screens for antiseizure properties, and the rotorod test assesses acute toxicity. Whereas antiseizure drug screening has been successful in bringing drugs to the market and improving our understanding of the pathophysiology of seizures, it merits emphasis that the vast majority of drug screening occurs in mature male rodents and involves models of seizures, not epilepsy. Effective drugs in acute seizures may not be effective in chronic models of epilepsy. Seizure type, clinical and electroencephalographic phenotype, syndrome, and etiology are often quite different in children with epilepsy than in adults. Despite these age-related unique features, drugs used in children are generally the same as those in adults. As awareness of the unique features of seizures during development increases, more drug screening in the immature animal will likely occur.
MeSH term(s)	Animals ; Anticonvulsants/pharmacology ; Anticonvulsants/therapeutic use ; Biomedical Research ; Disease Models, Animal ; Epilepsy/classification ; Epilepsy/drug therapy ; Humans ; Models, Biological
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2008-01-31
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	639164-3
ISSN	1873-5150 ; 0887-8994
ISSN (online)	1873-5150
ISSN	0887-8994
DOI	10.1016/j.pediatrneurol.2007.09.008
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Zs.A 2260: Show issues

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Article ; Online: Anticonvulsant effect of Cicer arietinum seed in animal models of epilepsy: introduction of an active molecule with novel chemical structure.

Sardari, Soroush / Amiri, Motahareh / Rahimi, Hourieh / Kamalinejad, Mohammad / Narenjkar, Jamshid / Sayyah, Mohammad

Iranian biomedical journal

2015 Volume 19, Issue 1, Page(s) 45–50

Abstract: ... animal models of epilepsy.: Methods: Dichloromethane extract was obtained from C. arietinum seeds ... The crude extract had neither toxicity up to 7 g/kg nor protective activity in MES and kindling models ... Phytochemical screening revealed the presence of considerable amount of alkaloids in the extract and fractions ...

Abstract	Background: Cicer arietinum (Chickpea) is one of the most important harvests in the world with high nutritional value. Lack of essential oils in the seeds of Chickpea is an advantage in search for drug-like molecules with less toxicity. We evaluated anticonvulsant effect of C. arietinum in common animal models of epilepsy. Methods: Dichloromethane extract was obtained from C. arietinum seeds by percolation. Acute toxicity of the extract was assessed in mice. Protective effect of the extract was examined against tonic seizures induced by maximal electroshock (MES; 50 mA, 50 Hz, 1 s) in mice, clonic seizures induced by pentylenetetrazole (PTZ; 60 mg/kg, i.p.) in mice, and electrical kindling model of complex partial seizures in rats. The extract was fractionated by n-hexane to f1 and f2 fractions. The extract and fractions underwent phytochemical analysis by thin layer chromatography. The active anticonvulsant fraction, f1, was subjected to matrix assisted laser desorption/ionization (MALDI) mass analysis. Results: The crude extract had neither toxicity up to 7 g/kg nor protective activity in MES and kindling models. However, it significantly inhibited clonic seizures induced by PTZ. f1 fraction mimicked protective effect of the extract. Phytochemical screening revealed the presence of considerable amount of alkaloids in the extract and fractions. Moreover, a novel structural class was detected in f1 fraction. Conclusion: Finding an anticonvulsant molecule pertaining to a new structural class in the seeds of C. arietinum promises an effective and inexpensive source of antiepileptic medication. Further studies are needed to identify its mechanism of action and more clues into its structure-activity relationship.
MeSH term(s)	Animals ; Anticonvulsants/therapeutic use ; Cicer/metabolism ; Disease Models, Animal ; Electroshock/adverse effects ; Epilepsy/chemically induced ; Epilepsy/drug therapy ; Male ; Mice ; Pentylenetetrazole ; Plant Extracts/analysis ; Plant Extracts/therapeutic use ; Pregnanolone/analogs & derivatives ; Pregnanolone/chemistry ; Rats ; Rats, Wistar ; Seeds/metabolism ; Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization
Chemical Substances	Anticonvulsants ; Plant Extracts ; ganaxolone (98WI44OHIQ) ; Pregnanolone (BXO86P3XXW) ; Pentylenetetrazole (WM5Z385K7T)
Language	English
Publishing date	2015-01-16
Publishing country	Iran
Document type	Journal Article ; Research Support, Non-U.S. Gov't
ZDB-ID	2489282-8
ISSN	2008-823X ; 1028-852X
ISSN (online)	2008-823X
ISSN	1028-852X
DOI	10.6091/ibj.1391.2014
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Zs.A 6776: Show issues

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Article ; Online: Critical review of current animal models of seizures and epilepsy used in the discovery and development of new antiepileptic drugs.

Löscher, Wolfgang

Seizure

2011 Volume 20, Issue 5, Page(s) 359–368

Abstract: ... in AED discovery for >6 decades. It has been argued that these old models may identify only drugs ... which, at least in part, may be due to the fact that the same simple screening models, i.e., the maximal ... discovery and development need a conceptual shift that is moving away from using models that identify ...

Abstract	Animal models for seizures and epilepsy have played a fundamental role in advancing our understanding of basic mechanisms underlying ictogenesis and epileptogenesis and have been instrumental in the discovery and preclinical development of novel antiepileptic drugs (AEDs). However, there is growing concern that the efficacy of drug treatment of epilepsy has not substantially improved with the introduction of new AEDs, which, at least in part, may be due to the fact that the same simple screening models, i.e., the maximal electroshock seizure (MES) and s.c. pentylenetetrazole (PTZ) seizure tests, have been used as gatekeepers in AED discovery for >6 decades. It has been argued that these old models may identify only drugs that share characteristics with existing drugs, and are unlikely to have an effect on refractory epilepsies. Indeed, accumulating evidence with several novel AEDs, including levetiracetan, has shown that the MES and PTZ models do not identify all potential AEDs but instead may fail to discover compounds that have great potential efficacy but work through mechanisms not tested by these models. Awareness of the limitations of acute seizure models comes at a critical crossroad. Clearly, preclinical strategies of AED discovery and development need a conceptual shift that is moving away from using models that identify therapies for the symptomatic treatment of epilepsy to those that may be useful for identifying therapies that are more effective in the refractory population and that may ultimately lead to an effective cure in susceptible individuals by interfering with the processes underlying epilepsy. To realize this goal, the molecular mechanisms of the next generation of therapies must necessarily evolve to include targets that contribute to epileptogenesis and pharmacoresistance in relevant epilepsy models.
MeSH term(s)	Animals ; Anticonvulsants/adverse effects ; Anticonvulsants/chemical synthesis ; Anticonvulsants/therapeutic use ; Disease Models, Animal ; Drug Design ; Drug Discovery/trends ; Epilepsy/blood ; Epilepsy/drug therapy ; Humans ; Seizures/blood ; Seizures/drug therapy
Chemical Substances	Anticonvulsants
Language	English
Publishing date	2011-06
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Review
ZDB-ID	1137610-7
ISSN	1532-2688 ; 1059-1311
ISSN (online)	1532-2688
ISSN	1059-1311
DOI	10.1016/j.seizure.2011.01.003
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Zs.A 3573: Show issues

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Article: Genetic animal models of epilepsy as a unique resource for the evaluation of anticonvulsant drugs. A review.

Löscher, W

Methods and findings in experimental and clinical pharmacology

1984 Volume 6, Issue 9, Page(s) 531–547

Abstract: ... demonstrating the validity of this new petit mal model for anticonvulsant drug screening. Models with reflex ... differently to antiepileptic drugs and seem to provide interesting models for petit mal and grand mal epilepsy ... of epilepsy offer unique approaches to the evaluation of antiepileptic drugs used or usable in man. ...

Abstract	Genetic animal models of epilepsy comprise genetically predisposed animal species in which seizures either occur spontaneously or in response to sensory stimulation. The major advantage of these naturally occurring epilepsies in animals as models of human epilepsy is that they simulate the clinical situation more closely than any other experimental epilepsy. Models with idiopathic spontaneous recurrent seizures are epileptic dogs, tottering mice, and rats with spike-wave absence (petit mal) seizures. In dogs, the most common seizure type are generalized tonic-clonic (grand mal) seizures. Recent epidemiological and antiepileptic drug efficacy studies strongly suggest that epileptic dogs offer a valuable model for human grand mal epilepsy. In tottering mice, two types of spontaneous recurrent seizures occur: spike-wave absence seizures and focal motor seizures. Both types differ in sensitivity to common antiepileptic drugs, which closely resembles the absence and focal types of epilepsy in humans. Spontaneously recurrent spike-wave absence seizures in rats can be selectively blocked by drugs effective in petit mal (absence) epilepsy in man, demonstrating the validity of this new petit mal model for anticonvulsant drug screening. Models with reflex seizures comprise photosensitive baboons (Papio papio) and fowl, audiogenic seizure susceptible mice and rats, and gerbils with seizures in response to different sensory stimuli. With respect to seizure types and drug efficacies in these species, rats and chickens may represent suitable models for grand mal epilepsy, whereas baboons offer a useful model of photomyoclonic seizures. Gerbils can be subdivided into animals with minor (myoclonic) and major (mostly generalized tonic-clonic) seizures, which respond differently to antiepileptic drugs and seem to provide interesting models for petit mal and grand mal epilepsy in man. In conclusion, the data summarized in this review emphasize that genetic animal models of epilepsy offer unique approaches to the evaluation of antiepileptic drugs used or usable in man.
MeSH term(s)	Acoustic Stimulation ; Animals ; Anticonvulsants/pharmacology ; Chickens ; Disease Models, Animal ; Dogs ; Drug Evaluation, Preclinical ; Electroencephalography ; Epilepsy/drug therapy ; Epilepsy/genetics ; Epilepsy, Absence/genetics ; Gerbillinae ; Mice ; Mice, Neurologic Mutants ; Models, Genetic ; Papio ; Photic Stimulation ; Rats ; Seizures/genetics ; Species Specificity
Chemical Substances	Anticonvulsants
Language	English
Publishing date	1984-09
Publishing country	Spain
Document type	Journal Article ; Review
ZDB-ID	446847-8
ISSN	2013-0155 ; 0379-0355
ISSN (online)	2013-0155
ISSN	0379-0355
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Zs.A 1525: Show issues

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Article: Modèles animaux d'épilepsie et crises expérimentales.

Bizière, K / Chambon, J P

Revue neurologique

1987 Volume 143, Issue 5, Page(s) 329–340

Abstract: Animal models of epilepsy are essential for the search of new effective antiepileptic drugs ... in animals. This, however, precludes finding new drugs for resistant epilepsies. Animal models of epilepsy ... widely used as simple and rapid screening systems for new anticonvulsant compounds. Moreover, the use ...

Title translation	Animal models of epilepsy and experimental seizures.
Abstract	Animal models of epilepsy are essential for the search of new effective antiepileptic drugs. Moreover they may lead to the discovery of the basic neuronal dysfunction(s) which underlies human epilepsies. Animal epilepsies as well as experimental seizures are usually considered as valid models of human epilepsies when, and only when, the drugs which are effective in human epilepsies prevent seizures in animals. This, however, precludes finding new drugs for resistant epilepsies. Animal models of epilepsy can be classified as follows: (i) experimental seizures induced by convulsant drugs or by an electrical stimulation; (ii) reflex epilepsies; (iii) idiopathic epilepsies. Examples of animal models of epilepsy taken from each of these three classes are briefly reviewed. Seizures induced by convulsant drugs or by an electroshock are widely used as simple and rapid screening systems for new anticonvulsant compounds. Moreover, the use of chemical convulsants can lead to new hypotheses concerning the mechanisms underlying human epilepsies. Thus, one of the main arguments in favor of the GABAergic hypothesis of epilepsy is that GABA antagonists induce seizures which are readily counteracted by most antiepileptic drugs. Among the other models of experimentally induced seizures, the kindling model is usually considered, on the basis of its pharmacological characteristics, as a Grand Mal type epilepsy model. Thirty years after this model was first described, the exact modifications induced in the brain by the kindling procedure remain unknown. Various animal species exhibit reflex epilepsies. Myoclonic seizures can be induced by photic stimulation in Papio-papio baboons; tonic-clonic seizures can be induced by various auditory stimuli in certain strains of mice and rats; myoclonic and tonic-clonic seizures can be induced by a variety of environmental stimuli in the mongolian gerbil; photosensitive and febrile seizures have been described in fowl. Most antiepileptic drugs are effective in these reflex epilepsies. Alterations in several neurotransmitter systems have been reported in susceptible strains as compared to resistant strains, such as modifications in noradrenergic, serotoninergic, GABAergic or glutamatergic transmissions, but no single abnormal parameter can unequivocally be correlated to seizure susceptibility. Idiopathic epilepsy is not uncommon in dogs and the prevalence of the disease appears to be comparable to that observed in man. Grand Mal type epilepsy appears to be the most frequent type of epilepsy in dogs; little work has been devoted to the study of the neurochemical alterations which may underly the disease.
MeSH term(s)	Acoustic Stimulation ; Animals ; Chickens ; Convulsants ; Disease Models, Animal ; Dogs ; Electric Stimulation ; Epilepsies, Partial ; Epilepsy ; Gerbillinae ; Mice ; Papio ; Photic Stimulation ; Rats
Chemical Substances	Convulsants
Language	French
Publishing date	1987
Publishing country	France
Document type	English Abstract ; Journal Article ; Review
ZDB-ID	4593-7
ISSN	2213-0004 ; 0035-3787
ISSN (online)	2213-0004
ISSN	0035-3787
Database	MEDical Literature Analysis and Retrieval System OnLINE

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