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Background & Aims: Animal models provide crucial tools to study epilepsy which is one of the most common neurological disorder. Experimental models are valid and essential to discover new antiepileptic drugs as well as to elucidate circuitry dysfunction of disease. Therefore, in this review, we summarize the prominent used methods for induction experimental seizures and epilepsy induced by electrical, chemoconvulsants, traumatic brain injury, acoustic stimulation as well as hyperthermia and hypoxia condition. Material and Methods: In this review data were collected through searching electronic databases of PubMed and Google Scholar for several methods of induction seizure and epilepsy in experimental animals. Results: The maximal electroshock (MES), pentylentetrazole (PTZ), and 6-Hz seizure models are three simple seizure models for inducing acute seizure in intact animal. The pilocarpine, kainic acid, antibiotics, metals and organophosphorus compounds have epileptogenic potency for inducing motor seizures. The most common type of chronic models of epilepsy are electrical kindling, PTZ-induced kindling and transgenic models. Pharmacoresistance models include the phenytoin- or lamotrigine-pretreated kindled rats model, the 6-Hz mouse model, pentylentetrazole induced seizures in rats pre-exposed to pilocarpine and intrauterine exposure of rats to methylazoxymethanol. Lastly, Posttraumatic epilepsy, audiogenic seizures, hyperthermia and neonatal hypoxia model as well as in vitro models are used to induce and study seizures. Conclusion: Epilepsy and seizure in experimental animals can be modeled by several factors include acute and chronic stimulation, mechanical insults and changing environmental conditions in both forms in vivo and vitro.

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Background: Anxiety is a common ailment of high co-morbidity with epilepsy, a chronic neurologic disease characterized by recurrent seizures. Current drugs used for these conditions have several limitations such as disabling side effects, relapse, and ineffectiveness in certain population necessitating the search for alternative options. The aqueous leaf extract of Cymbopogon citratus (CYC) is widely used for its various health-promoting effects including relief of seizures and anxiety in ethnomedicine. This present study describes its effects on convulsions, anxiety-like behaviors, and social interaction in mice. Methods: Male Swiss mice were pretreated orally with CYC (25, 50, and 100 mg/kg), diazepam (1 mg/kg), or distilled water (10 mL/kg) 60 min before induction of convulsions with intraperitoneal (i.p.) injection of picrotoxin (10 mg/kg), pentylenetetrazole (PTZ; 85 mg/kg), or isoniazid (300 mg/kg). The animals were then observed for the occurrence of seizure for 30 min or 2 h for isoniazid. The effects of CYC on anxiety-like behaviors, social interaction, and spontaneous motor activity (SMA) were evaluated in naive mice. Results: CYC (25-100 mg/kg) did not prevent convulsions nor delay the latency to convulsions induced by picrotoxin, PTZ, or isoniazid. Pretreatment with CYC (50 and 100 mg/kg, p.o) produced anxiolytic-like effect, decreased SMA, and also enhanced social interaction behavior in naive mice. Conclusions: The results of this study suggest that CYC did not exhibit an anticonvulsant property in mice injected with picrotoxin, PTZ, or isoniazid, but its anxiolytic-like activity and social interaction-promoting effect might be of benefit as an adjuvant in improving the quality of life of epileptic patients. [ABSTRACT FROM AUTHOR]

The use of zebrafish as a model organism is gaining evidence in the field of epilepsy as it may help to understand the mechanisms underlying epileptic seizures. As zebrafish assays became popular, the heterogeneity between protocols increased, making it hard to choose a standard protocol to conduct research while also impairing the comparison of results between studies. We conducted a systematic review to comprehensively profile the chemically-induced seizure models in zebrafish. Literature searches were performed in PubMed, Scopus, and Web of Science, followed by a two-step screening process based on inclusion/exclusion criteria. Qualitative data were extracted, and a sample of 100 studies was randomly selected for risk of bias assessment. Out of the 1058 studies identified after removing duplicates, 201 met the inclusion criteria. We found that the most common chemoconvulsants used in the reviewed studies were pentylenetetrazole (n = 180), kainic acid (n = 11), and pilocarpine (n = 10), which increase seizure severity in a dose-dependent manner. The main outcomes assessed were seizure scores and locomotion. Significant variability between the protocols was observed for administration route, duration of exposure, and dose/concentration. Of the studies subjected to risk of bias assessment, most were rated as low risk of bias for selective reporting (94%), baseline characteristics of the animals (67%), and blinded outcome assessment (54%). Randomization procedures and incomplete data were rated unclear in 81% and 68% of the studies, respectively. None of the studies reported the sample size calculation. Overall, these findings underscore the need for improved methodological and reporting practices to enhance the reproducibility and reliability of zebrafish models for studying epilepsy. Our study offers a comprehensive overview of the current state of chemically-induced seizure models in zebrafish, highlighting the common chemoconvulsants used and the variability in protocol parameters. This may be particularly valuable to researchers interested in understanding the underlying mechanisms of epileptic seizures and screening potential drug candidates in zebrafish models. • We systematically reviewed the effects of chemically-induced seizures in zebrafish. • PTZ is the most commonly used epileptic seizure inducer in zebrafish. • More than 50% of studies fail to report outlier exclusion and sample size estimation. • The results showed a need for better standardization of protocols. [ABSTRACT FROM AUTHOR]

Using effector analysis, we studied the mechanism of anti-seizure activity of the alcoxy-derived benzodiazepine (propoxazepam). In models of chemically induced seizures we determined the average molar and weight effective doses (ED) of propoxazepam as an antagonist of picrotoxin (4.10 ± 0.21 μmol/kg, 1.67 ± 0.09 mg/kg), pentylenetetrazole (2.24 ± 0.93 μmol/kg, 0.9 ± 0.04 mg/kg), and strychnine (40.33 ± 14.91 μmol/kg, 14.24 ± 0.47 mg/kg), which reflect the high activity level of the substance. On the basis of dose-effect curves, using comparative quantile analysis for chemoconvulsants with different mechanisms of action, we showed different stages of interaction of propoxazepam with GABA and glycine receptors under in vivo conditions. We evaluated the partial contribution of myoclonic and toxic components to the general structure of seizures induced by various chemoconvulsants. We believe that the results we obtained indicate that the anti-seizure action of propoxazepam is predominantly mediated by a GABAergic mechanism. Glycinergic components of the inhibition of strychnine-induced seizures by propoxazepam occur at doses that exceed the ED and seem to be an additional means of anti-seizure action. [ABSTRACT FROM AUTHOR]

Abstract: Larval zebrafish (Danio rerio) have recently been suggested as a high-throughput experimental model of epilepsy-related pathogenetic states. Here we use adult zebrafish to study behavioral symptoms associated with drug-evoked seizures. Experimental epilepsy-like states were evoked in zebrafish by exposure for 20min to three chemoconvulsant drugs: caffeine (250mg/L; 1.3mM), pentylenetetrazole (1.5g/L; 11.0mM) and picrotoxin (100mg/L; 0.17mM). Fish behavior was analyzed using manual and video-tracking methods (Noldus Ethovision XT7). Compared to their respective controls, all three drug-treated groups showed robust seizure-like responses (hyperactivity bouts, spasms, circular and corkscrew swimming) accompanied by elevated whole-body cortisol levels (assessed by ELISA). In contrast, control fish did not display seizure-like behaviors and had significantly lower cortisol levels. Paralleling behavioral and endocrine phenotypes observed in clinical and rodent studies, our data implicates adult zebrafish as an emerging experimental model for epilepsy research. [ABSTRACT FROM AUTHOR]

To define their efficacy and mechanism of action, the possible antagonistic effects of intravenously administered dextrorphan and dizocilpine, non-competitive N-methyl- d-aspartic acid (NMDA) receptor antagonists, on tonic convulsions and death in a variety of experimental mice models were compared. Dextrorphan not only produced dose-dependent protection against the tonic convulsions caused by an intracerebroventricular injection of NMDA, but also showed a broad spectrum of anticonvulsant activities against tonic convulsions caused by α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA), kainic acid (KA), bicuculline, pentylenetetrazole or electroconvulsive shock. The anticonvulsant action of dizocilpine was found to be more efficacious for any type of tonic convulsions and was 20- to 70-fold more potent than that of dextrorphan. Dizocilpine, unlike dextrorphan, impaired motor function at doses showing its anticonvulsant activity. Bay k-8644 (a Ca channel agonist)-induced seizures were not antagonized by dextrorphan. Dextrorphan and dizocilpine were characteristically selective for protective functions against death, especially with three subtypes of glutamate receptors, as death caused by NMDA but not by AMPA and KA was selectively and markedly inhibited by both dextrorphan and dizocilpine. In view of these results, the efficacy of dextrorphan and dizocilpine as antagonists of convulsant effects appears to be consistent with the interpretation that a variety of convulsants cause tonic convulsions via direct or indirect interaction with the NMDA receptor complex. Furthermore, it is suggested that influx of Ca and intracellular Ca activity, such as the Bay k-8644-modulated activation of Ca binding proteins, are not directly modified by the administration of dextrorphan, itself. [ABSTRACT FROM AUTHOR]

Background Anxiety is a common ailment of high co-morbidity with epilepsy, a chronic neurologic disease characterized by recurrent seizures. Current drugs used for these conditions have several limitations such as disabling side effects, relapse, and ineffectiveness in certain population necessitating the search for alternative options. The aqueous leaf extract of Cymbopogon citratus (CYC) is widely used for its various health-promoting effects including relief of seizures and anxiety in ethnomedicine. This present study describes its effects on convulsions, anxiety-like behaviors, and social interaction in mice. Methods Male Swiss mice were pretreated orally with CYC (25, 50, and 100 mg/kg), diazepam (1 mg/kg), or distilled water (10 mL/kg) 60 min before induction of convulsions with intraperitoneal (i.p.) injection of picrotoxin (10 mg/kg), pentylenetetrazole (PTZ; 85 mg/kg), or isoniazid (300 mg/kg). The animals were then observed for the occurrence of seizure for 30 min or 2 h for isoniazid. The effects of CYC on anxiety-like behaviors, social interaction, and spontaneous motor activity (SMA) were evaluated in naive mice. Results CYC (25-100 mg/kg) did not prevent convulsions nor delay the latency to convulsions induced by picrotoxin, PTZ, or isoniazid. Pretreatment with CYC (50 and 100 mg/kg, p.o) produced anxiolytic-like effect, decreased SMA, and also enhanced social interaction behavior in naive mice. Conclusions The results of this study suggest that CYC did not exhibit an anticonvulsant property in mice injected with picrotoxin, PTZ, or isoniazid, but its anxiolytic-like activity and social interaction-promoting effect might be of benefit as an adjuvant in improving the quality of life of epileptic patients.

Piperine, a natural compound isolated from the fruits of Piper, is known to modulate several neurotransmitter systems such as serotonin, norepinephrine, and GABA, all of which have been linked to the development of convulsions. Fruits of Piper species have been suggested as means for managing seizure disorders. The present study was designed to elucidate the anticonvulsant effect of piperine and its mechanisms of action using in-silico, in-vivo and in-vitro techniques.PASS software was used to determine its possible activity and mechanisms. Furthermore the latency for development of convulsions and mortality rate was recorded in different experimental mouse models of epilepsy (pentylenetetrazole, maximal electroshock, NMDA, picrotoxin, bicuculline, BAYK-8644, strychnine-induced convulsions) after administration of various doses of piperine (5, 10 and 20 mg/kg, i.p.). Finally, the effect of piperine on Na(+) and Ca(2+) channels were evaluated using the whole cell patch clamp techniqueOur results revealed that piperine decreased mortality in the MES-induced seizure model. Moreover, piperine (10 mg/kg) delayed the onset of tonic clonic convulsions in the pentylenetetrazole test and reduced associated mortality. Furthermore, an anticonvulsant dose of piperine also delayed the onset of tonic clonic seizures in strychnine, picrotoxin and BAY K-8644. Complete protection against mortality was observed in BAYK-8644 induced convulsions. Finally, whole cell patch clamp analysis suggested an inhibitory effect of piperine on Na(+) channels. Together, our data suggest Na(+) channel antagonist activity as a contributor to the complex anticonvulsant mechanisms of piperine.