Aging Models of Acute Seizures and Epilepsy

Abstract

Aged animals have been used by researchers to better understand the differences between the young and the aged brain and how these differences may provide insight into the mechanisms of acute Models of Acute Seizures in Aged MiceIn aged animals, the most commonly used models employ electrical stimulation or a convulsant agent, such as kainic acid, pilocarpine, or pentylenetetrazol, to induce acute seizures. Depending on the model and the animal strain used, the results of studies of acute seizures in aged animals have variably demonstrated increased or decreased seizure susceptibility associated with advanced age. Early studies, using the BDF1 mouse strain (a cross between female C57BL/6 and male DBA/2 mice), ex- plored the effect of aging on acute seizure susceptibility and demonstrated that the threshold for the tonic extensor component of maximal electroshock seizures increased with age (up to 30 months) (1). Similarly, the minimal effective concentration of pentylenetetrazol needed to induce maximal seizure activity increased in 24-month-old compared to 6-month-old animals (2), as did the sensitivity to the anticonvulsant effects of oxazepam (3) and phenobarbital in the same model (4). These studies suggested that aged BDF1 mice required increased levels of electrical or chemical stimulation to generate acute seizures, whereas decreased concentrations of anticonvulsants active at the GABA A receptor were required to mitigate pentylenetetrazol-induced maximal seizure activity.Except for early studies of BDF1 mice, which showed equivalent effects in both male and female animals (1-3), relatively few studies have assessed gender-based differences in seizure susceptibility and/or neurodegeneration in mice. A study of seizure susceptibility in adult and aged animals of the inbred CBA strain demonstrated that 3-month-old males were distinctly more prone to seizures induced by the GABA A receptor antagonists, bicuculline and picrotoxin, compared to age-matched females; picrotoxin-induced seizure latencies were also decreased in the male animal (5). However, there was no gender-based difference in sensitivity to picrotoxin in 24-month-old animals. Comparing adult and aged male and female C57BL/6J mice following kainic acid treatment, aged female mice demonstrated more severe seizure activity, prominent hippocampal injury, and increased astrocyte proliferation (6). In studies not based on gender but using the same C57BL/6J strain, acute seizures were induced by a single electroconvulsive shock, followed by assessment of c-fos expression in different brain regions of varying age groups. All ages exhibited a transient increase in c-fos immunoreactivity, but in aged animals, the response was significantly less robust (7). Following a single dose of kainic acid, aged C57BL/6J mice were more sensitive to its pathological effects compared to adult animals, especially with regard to neuroinflammatory changes, as measured by markers of reactive gliosis (8). Comparing young adult, mid-aged, and aged C57BL/6J mice to similarly...

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