2.1.4 Iron Induced Seizure Model
FeCl2 or FeCl3 iron injections induce chronic epileptogenic foci in the
rat cerebral cortex that discharges independently. This
experimental epileptogenic focus has been extensively studied to
understand the mechanism of clinical post-traumatic epilepsy and
GTCS. In their study by Sharma Varsha et al., 60 male Wistar
rats weighing 250–300 g were five mcL/ 100 mM [33]. Sharma
Varsha et al. focused on the iron-induced Model of post-traumatic
chronic focal epilepsy in rats. It aimed to investigate the
characteristics of epileptic events detected through electrocorticogram
(ECoG) recordings and their associated behavioral manifestations.
Epileptiform activity was observed chronically in the cortical and depth
recordings during wake behavior, starting around day eight post-iron
injection. Between day three and day 8, minimal epileptiform seizure
activity was detected in the EEG records. By day eight post-iron
injection, frequent electrical outbreaks, characterized by spike-wave
complexes, were evident. In later time points, such as day 18 and day
28, the recordings showed longer-duration electrical paroxysms,
including spike-wave complexes and poly spiking, both in cortical and
depth recordings.
- Advantages: A valuable framework for researching and
comprehending the mechanisms underlying epilepsy is provided by using
an iron-induced model of post-traumatic chronic focal epilepsy in
rats. This Model allows researchers to study the onset and progression
of human epilepsy by simulating some elements.
- Disadvantages: Most of the drugs are ineffective in reducing
iron-induced epilepsy, and only ethosuximide has been studied
- Mechanical/Electrical Models
- Maximal electroshock model
- Audiogenic seizure model
- Impact acceleration model
- Optogenetics
2.2.1 Maximal electroshock model
Maximal electroshock seizure (MES) is used to cause acute epileptic
behaviors. Adult mice or rats (those older than six weeks) are
often given an electrical stimulus. Mice and rats were given stimuli 50
mA and 150 mA, respectively. The pulse frequency is 50-60 Hz, pulse
width is 0.6 ms, and the stimulus duration is 0.2 ms. In the MES model,
roughly 3–10 times greater than the animal’s electrical seizure
threshold is administered [33] . The everyday MES actions
include Foaming at the mouth and urinary incontinence, followed by
hindlimb extension, falling, and back rigidity. Experimental
research on novel ASMs has primarily been conducted on healthy mice and
rats in which seizures were generated using chemicals or electricity for
practical reasons. The maximal electroshock seizure (MES) model has
persisted over time as one of the benchmarks for initial testing.
MES seizure score:
- No seizure
- Forelimb extension without hindlimb extension
- Complete forelimb extension and partial hindlimb extension
- Total Hindlimb extension
- Post ictal depression
- Advantages: The MES model predicts generalized tonic-clonic
seizures in animals because it causes highly repeatable seizures. This
predictability is necessary for determining whether a proposed ASM is
successful.
- Disadvantages: Different seizure types, like focal and
absence seizures, cannot be evaluated.
- Audiogenic Seizure ModelAudiogenic seizures (AGS), brought on by sound stimulation
(>30 dB), cause SUDEP in animal models[34] . The mouse exhibits a stereotyped behaviour right
after the sound is presented, including wild running, a clonic
seizure, a tonic-clonic seizure in which the mouse falls on its
flanks, and a tonic seizure with an extension of the limbs towards
the tail, which may or may not be followed by death. AGS in
129/SvTer mice is a valuable model for SUDEP because both SUDEP and
AGS share a respiratory mechanism of death since death can occur
during a seizure.
Advantages: SUDEP can be very well studied by this model, and
the mechanism almost mimics humans.
Disadvantages: Audiogenic seizure models are poorly
repeatable.