Epilepsia, 45(10):1219–1227, 2004 Blackwell Publishing, Inc. C  2004 International League Against Epilepsy Aging Alters Electroencephalographic and Clinical Manifestations of Kainate-induced Status Epilepticus ∗ Olivier Darbin, †Dean Naritoku, and ∗ Peter R. Patrylo ∗ Department of Physiology, Southern Illinois University School of Medicine, Carbondale, and †Departments of Neurology and Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois, U.S.A. Summary: Purpose: The elderly exhibit an increased risk for developing status epilepticus and status-related morbidity and mortality. However, it is unclear how aging alters the progres- sion of electroencephalographic (EEG) activity and behavioral manifestations during status epilepticus. Methods: A repetitive low-dose kainate treatment protocol (2.5 mg/kg/h; i.p.) was used in this study in conjunction with EEG and behavioral monitoring from freely behaving adult (7– 8 months) and aged (22–25 months) Fischer 344 rats to assess the effects of aging on status epilepticus. Results: During kainate treatment, both groups exhibited an increase in EEG power that corresponded with the time course of kainate treatment. However, visual inspection and spectral analysis revealed a reduction of the faster frequencies (12.5–35 Hz) in the EEGs of aged rodents. A similar progression of be- havioral manifestations was observed in adult and aged rodents during kainate treatment, although the frequency of preseizure manifestations (e.g., wet-dog shakes; aged rats, 110 events/h vs. adults, 25 events/h; median values) was greater, and latency to onset for any given behavioral manifestation (e.g., class V seizures; aged median, 60 min, vs. adult median, 145 min) was consistently shorter within the aged group. Conclusions: These data reveal that aged Fischer 344 rats ex- hibit altered EEG activity (reduction of higher frequencies) and clinical manifestations during kainate-induced status epilepti- cus. Taken together, these data indicate an age-related change in seizure onset and spread after exposure to glutamate ana- logues. Key Words: Geriatric—Kainic acid—Fischer 344— EEG—Seizure—Sustained seizure. Epidemiologic studies indicate that an increased inci- dence and prevalence for seizure disorders and epilepsy is found at the extremes of life (in young children and in the elderly), with the highest incidence observed among the elderly (1–4). Seizure disorders/epilepsy are the third most common neurologic disorder in the elderly (5), and it is be- lieved to be a major cause of morbidity and mortality (6,7). In particular, the elderly appear to have an increased risk for developing status epilepticus and status-related mor- bidity and mortality (6–10). Several age-related complica- tions (e.g., Alzheimer’s disease, stroke, tumors, electrolyte disturbances) are known to contribute to the increased in- cidence of epilepsy/seizure disorders in the elderly (11). However, epidemiologic studies have reported that ≤50% of cases of epilepsy/seizure disorders in the elderly have no identifiable antecedents; these cases are classified as idiopathic (11). This observation has led to the hypothesis that aging of the central nervous system itself may affect seizure susceptibility (11,12). Therefore additional infor- mation, including the development of animal models, is re- Accepted June 17, 2004. Address correspondence and reprint requests to Dr. P.R. Patrylo at De- partment of Physiology, Southern Illinois University School of Medicine, Carbondale, IL 62901, U.S.A. E-mail: ppatrylo@siumed.edu quired to understand all of the antecedents associated with the age-related increase in seizure susceptibility/severity. Whether rodents exhibit a similar increase in seizure susceptibility/severity during aging is debatable, because of the contradictory nature of available data (13–18). For example, the rate of kindling has been reported to be slower in aged rodents relative to adults (13,17). How- ever, aged rodents exhibit longer-duration afterdischarges throughout the kindling process and a faster propagation of the afterdischarge to the contralateral side (17). Ad- ditionally, whereas aged mice have been suggested to have an increased threshold to pentylenetetrazol (PTZ)- induced seizures (14), aged rats exhibit a higher inci- dence and longer duration of generalized convulsions after PTZ administration relative to adults (17). Several stud- ies have noted an enhanced vulnerability to domoic acid or its structural analogue kainate (both known convulsive agents) in elderly humans and aged rodents (15,16,19– 21). Nevertheless, it is unclear whether the progression of the EEG activity and behavioral manifestations as- sociated with status epilepticus is altered during aging. In the present study, a multi-low-dose kainate-treatment protocol (22,23) was used in conjunction with com- bined behavioral/EEG monitoring to examine the gradual 1219