Chapter 41 - Poststatus Epilepticus Models: Focal Kainic Acid

Abstract

Focal injection of the potent excitotoxin kainic acid into various brain structures elicits status epilepticus (SE), and the later development of epilepsy in experimental animals. Two of the most studied models involve injection of kainic acid into the hippocampus or amygdala of rats and mice. Intrahippocampal kainic acid produces unilateral hippocampal sclerosis comprising extensive neuron loss, gliosis, dispersion of dentate granule neurons, and mossy fiber sprouting along with spontaneous recurrent seizures that are mainly focal and nonconvulsive. The model has a number of attendant features, including hippocampal learning and memory deficits, and the spontaneous seizures are refractory to several antiepileptic drugs. Intraamygdala kainic acid produces a more limited hippocampal lesion that features neuron loss and gliosis but other pathological hallmarks are less overt. Spontaneous seizures emerge within a few days of SE in the intraamygdala model and feature focal limbic, as well as secondarily generalized convulsive behaviors. Both models feature low morbidity and mortality. Variations of these models in mice have proven particularly successful for exploring the genetic contribution to cell and molecular mechanisms of temporal lobe epilepsy and identifying potential disease-modifying treatments.