Abstracts

Epidemiological studies have demonstrated an increased incidence and prevalence for seizure disorders in the elderly; approximately 25% of all newly reported cases of seizure disorders are in people 60 or older. A conservative estimate ranks epilepsy as the third most common neurological disorder in the elderly (after stroke and dementia) and it is a major cause of morbidity and mortality. However, it is unclear how aging alters the clinical manifestations (i.e. behavioral seizures) and paroxysmal activities (i.e. EEG epileptiform activity) during the progression into convulsive status. In the present study, a repetitive low-dose kainate-treatment protocol was used in conjunction with behavioral and EEG monitoring to examine the gradual progression of seizures and status epilepticus in freely-behaving aged and adult Fischer 344 rats.
Male Fischer 344 rats (3-6 months or 24-26 months) were anesthetized and then implanted stereotaxically with surface EEG and hippocampal depth electrodes. One week later, freely-behaving rats were treated with kainic acid (2.5mg/kg/hr; IP). Treatment continued until the onset of sustained convulsive seizures.
During kainate-treatment a progression of behavioral manifestations was elicited that entailed: wet-dog shakes, a decrease in voluntary locomotor and motor activity (LMA), automations (Class I, II, III according to a modified Racine[apos]s scale) generalized convulsions (Class IV, V), and finally status epilepticus. During status epilepticus, the severity of behavior manifestations also progressed in a stereotypical pattern and correlated with the duration of treatment. While similar behavioral manifestations were observed in both adult (n = 4) and aged (n = 4) rats, the time to onset for any given behavioral characteristic (e.g., class III seizures) was consistently quicker in the aged animals (p [le] 0.05 for each behavioral manifestation). Examination of EEG activity revealed that an increase in beta band frequency (12-35 Hz) occurred in adult rats during kainate-treatment. This increase in beta band frequency was significantly attenuated in aged rats (p [le] 0.05).
Although preliminary, these data suggest that aging is associated with an increased susceptibility for seizure generation following administration of kainic acid. Furthermore, the attenuation of 12-35 Hz activity (EEG) in aged rats, relative to adults, during the progression of kainate-induced status suggests that there maybe an aging-related modification in neuronal synchronization. The elderly comprise the fastest growing segment of the population, and estimates suggest that by the early part of this century 20% of the population will be older than 65. Thus, beginning to understand the changes that occur within the central nervous system during aging will be essential in helping curtail/prevent this growing health concern.
[Supported by: NIH grant AG00795]