In Vivo Models

6.11.4.2.1 Induced models

6.11.4.2.1.1 Chemically induced seizures

Seizures can be induced in rodents using a variety of chemicals. These include pentylenetetrazole (PTZ), strychnine, picrotoxin, the GABAa antagonist bicuculline, the GABAa receptor inverse agonist methyl 6,7-dimethoxy-4-ethyl-b-carboline-3-carbonylate, glutamate antagonists, e.g. kainiate, domoic acid, NMDA, quisqualate, the potassium channel blockers 4-aminopyridine and dendrotoxin (DTX), the latter a snake venom given i.c.v., and glutamic acid decarboxylase (GAD) inhibitors.

6.11.4.2.1.2 Maximal electroshock (MES)

Maximal electroshock (MES) in mouse or rat is a widely used model of epilepsy. A 60 Hz alternating current is applied by corneal electrodes and is one of the more widely used models.

6.11.4.2.1.3 Kindled mice

Kindling, a seizure-induced plasticity of the nervous system, can be evoked in rats by repeated administration of a subconvulsive electrical stimulus via bipolar electrodes implanted in the amygdala, hippocampus, or entorhinal cortex which leads, after a few days, to secondarily generalized seizures that eventually become spontaneous reflecting a model of mesial temporal lobe epilepsy (MTLE).9 Mice can similarly be kindled with kainate to provide a model of MTLE. The latter is characterized by frequent seizures initiated from the temporal lobe and is associated with hippocampal sclerosis, neuronal loss, and gliosis. Kindling can also be achieved using cobalt or Fe3 + implants. Kindled mice show neuronal loss in the hippocampus, e.g., CA1, CA3 regions, with spontaneous and reccurrent hippocampal discharge. Like MTLE in humans, the kainiate kindled mouse model is resistant to most AEDs.

6.11.4.2.1.4 Status epilepticus

Status epilepticus can be induced in mice with pilocarpine, lithium-pilocarpine, kainiate, or electrical stimulation of amygdala, perforant pathway, or hippocampus. Such animals develop spontaneous seizures after a latent period.

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