Figure [1]: This diagram shows the classification of many
animal epilepsy models, including Generalised Tonic-Clonic Seizure
(GTCS), Absence Seizure, Myoclonus, and Status Epilepticus models, along
with their subtypes.
Animal models of epilepsy or seizures in the research and development of
ASMs,
- The discovery of new ASMs,
- The characterization of the anticonvulsant activity of new ASMs,
- Specific models for drug-resistant seizures,
- The assessment of whether the efficacy of new ASMs changes during
chronic treatment,
- The comparison of adverse effects of new ASMs in animals with epilepsy
versus those without epilepsy and the estimation of effective plasma
concentrations of new ASMs for initial clinical trials are examples.
- Discovery of disease-modifying or antiepileptogenic drugs discovery of
disease-modifying or antiepileptogenic therapies [18].
- In Vitro Model
Studying epilepsy and epileptic convulsions using in vitro preparations
is worthwhile and practical. From practically any species, these
preparations can be obtained [19] . Mammalian brain slices
are the method that researchers employ the most frequently when looking
at epileptiform activity. These thin brain slices can either be employed
immediately (the acute brain slice preparation) or after being preserved
in culture for several days or weeks in an incubator (the organotypic
brain slice preparation) [20] .
Brain preparations from various mammalian species, including rabbits,
guinea pigs, rats, mice, and humans after neurosurgical resections, have
induced in vitro epileptiform activity [21] . The most often
used species has been rats, and several strains have been used. However,
the appeal of using mouse models for experiments has grown due to the
relatively simple process of altering the mouse genome and the recent
widespread usage of transgenic mouse strains. Differing mouse strains
exhibit differing sensitivity to epileptogenic circumstances or might
have developmental flaws or other traits due to their varied genetic
backgrounds. Rats and other rodent species behave similarly[22] .
The age of the animal from which brain tissue is obtained significantly
impacts the appearance of epileptiform activity in vitro[23] . However, it is unclear how an animal’s age affects
how easily they can induce seizure-like episodes in vitro[24] . For instance, using the high K+ model, seizure-like
events are not elicited in tissue from animals younger than postnatal
day 5 (P5) in rat hippocampus slices. These are easiest to evoke at P12
before becoming challenging to create in animal tissue beyond P21[23] . Age-related variations in excitability and seizure
propensity are controlled by several different processes, which leads to
such complexity. As one illustration, GABAergic signaling is
hypothesized to depolarize early in development compared to adult tissue
because of high amounts of intracellular chloride [25] .
Remembering that different species, strains, and sexes have varied
maturational trajectories and alterations in various signaling pathways
is crucial. At P7–P12, Rat and mouse pups are compared to newborn
humans in terms of development. Experimental groups have to be
appropriately randomized for the ages of the animals, and the impact of
age is correctly accounted for in study statistics and reported in
published manuscripts [26] .
In Vivo Models
To elucidate the neurochemical, neurophysiological, cellular, and
molecular mechanisms that control epileptic seizures, several
experimental models have been created in which epileptic activity is
replicated and various treatments are explored. Studies on these models
have also helped search for pathways similar to those that cause real
epilepsy. The various animal models can be grouped into convulsively
induced chemically, such as penicillin and cobalt, electrically, such as
kindling and electroshock, or genetically, such as audiogenic seizures[27] . Scientists and researchers work to understand the
mysteries of life and the intricacies of diseases and to create novel
remedies in the field of biomedical research. In vivo models, which
bridge the gap between in vitro experiments and clinical trials, are
crucial in this endeavor. In vivo models frequently involve living
things and provide unique benefits for examining biological processes,
disease mechanisms, and prospective therapeutic approaches.
Although these models have tried to explain the underlying mechanics of
this condition precisely, the cause of the development of so many
distinct varieties of epilepsy has not yet been identified. Partial
epilepsy, tonic-clonic convulsions, and status epilepticus (SE) were the
three categories Fisher proposed for an epileptogenic classification of
models in 1989. This review comprises the most prevalent in vivo
epileptogenesis models currently understood by this classification.
Fisher’s classification of epilepsy models, as modified for this review,
only refers to in vivo models [28] . See
Figure 1.