Investigations of epilepsy with a mutant animal (EL mouse) model.
OBJECTIVE
The EL mouse model, with running fits and convulsions, has been useful for studying mechanisms of epilepsy, epileptogenesis, and ictogenesis.


METHODS
The history of this model and recent key findings are described.


RESULTS
Epileptogenesis has a hereditary component, and the genes responsible for it are presumed to be multiple. A seizure of an EL animal is precipitated by a rapid accelerating movement. Seizures develop in conjunction with aging of the mouse, repetition of stimuli, and with seizures themselves. This phenomenon represents a type of abnormal plasticity, which underlies epileptogenesis. The paroxysmal discharges in EL begin at parietal cortex, propagate to hippocampus, and then to the entire brain. Manifestation of a seizure requires a combination of several brain regions, termed the "focus complex." A small but significant disorganization of hippocampal cytoarchitecture occurs, leading to higher excitability. Abnormally low GABAergic function in the parietal cortex and hippocampus develops with maturation of the EL mouse and with repetition of stimuli and seizures. Low superoxide dysmutase activity and abnormal eNOS function in hippocampus or parietal cortex may relate to epileptogenesis of EL. After seizures, immediate early genes (e.g., c-fos and zif) expression and DNA fragmentation are observed, which play important roles in ictogenesis and epileptogenesis. All of these phenomena follow a process of development similar to that of the seizure itself.


CONCLUSIONS
Insights from the EL model suggest that epileptogenesis and ictogenesis in epilepsy can be viewed in terms of genetic predisposition and a new concept of abnormal plasticity.
Suzuki
Jiro
J
Organized Center of Clinical Medicine, Department of Health and Welfare, International University of Health and Welfare, Ohtawara, Tochigi, Japan. jsuzuki@iuhw.ac.jp
D000818:Animals; D001921:Brain / Q000378:metabolism / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004827:Epilepsy / Q000235:genetics* / Q000378:metabolism / Q000503:physiopathology; D006624:Hippocampus / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008818:Mice, Neurologic Mutants / Q000235:genetics*; D009434:Neural Pathways / Q000378:metabolism / Q000503:physiopathology; D009473:Neuronal Plasticity / Q000235:genetics / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000378:metabolism / Q000502:physiology; D005680:gamma-Aminobutyric Acid / Q000502:physiology
D005680:gamma-Aminobutyric Acid; D019001:Nitric Oxide Synthase