A model of atypical absence seizures: EEG, pharmacology, and developmental characterization.
OBJECTIVE
Atypical absence seizures differ markedly from typical absence seizures in EEG findings, ictal behavior, and neurodevelopmental outcome. The object of these experiments was to provide electrical, behavioral, pharmacologic, and developmental characterization of a putative animal model of atypical absence seizures.


METHODS
Atypical absence seizures were induced in Long Evans hooded rats by treatment with a cholesterol biosynthesis inhibitor, AY-9944 (AY), during development. Prolonged video EEG recordings were made from chronically implanted depth electrodes in the waking and sleep states in adult and developing animals during and after AY treatment. Also, the response of AY-induced atypical absence seizures to drugs known to exacerbate and block typical absence seizures was ascertained.


RESULTS
AY treatment resulted in spontaneous, bilaterally synchronous, slow spike-and-wave discharges (SWD), which were frequent, recurrent, prolonged, and lifelong. SWD began as early as postnatal day 21, occurred throughout all stages of sleep, and were associated with myoclonic jerks during sleep. The SWD were significantly prolonged by carbamazepine, gamma-hydroxybutyrate, and the gamma-aminobutyrate type B (GABA(B)) receptor (GABA(B)R) agonist baclofen. AY-induced seizures were abolished by diazepam, ethosuximide, and the GABA(B)R antagonist CGP 35348 but returned as the drugs were eliminated. Atypical features of absence seizures in this model are slow spike-wave, emanation of SWD from hippocampus, gradual onset and offset of ictal behavior, and the ability of the animals to move during the spike-and-wave bursts.


CONCLUSIONS
The AY-treated rat represents a predictable, reproducible, and clinically relevant animal model of atypical absence seizures that may be used to investigate the pathogenesis and treatment of this malignant disorder.
Cortez
M A
MA
Brain and Behavior Program and Bloorview Epilepsy Program, Division of Neurology, Hospital for Sick Children, Toronto, Ontario, Canada.
McKerlie
C
C
Snead
O C
OC
D000818:Animals; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004569:Electroencephalography; D004832:Epilepsy, Absence / Q000473:pathology / Q000503:physiopathology*; D005260:Female; D008297:Male; D051381:Rats; D020318:Rats, Long-Evans; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar