Abstracts

Rationale: Circadian rhythms are endogenously mediated behavioral activities with a 24 hour cycle. Acute and chronic seizures are modulated by circadian rhythms both in human and animal models of epilepsy, which may be due to differential neuronal excitability during sleep and wake states. However, whether acute or chronic seizures modulate circadian rhythm expression has not been well studied. We hypothesized that circadian rhythms of behavior and locomotion are altered in animal model of limbic epilepsy.Methods: Twenty two male Sprague-Dawley rats (250-280 g) were implanted with 4 epidural screw electrodes. One week subsequent to surgical implantation, status epilepticus (SE) was induced with lithium/pilocarpine. EEG was continuously recorded during SE and was stopped with diazepam (DZM) plus phenobarbital (PB) at various EEG-defined stages of status epilepticus. One week Post-SE, animals were continuously monitored with EEG, for 12 weeks in order to detect onset and frequency of subsequent seizures. Animals were then classified into epileptic and control groups depending on whether or not they developed spontaneous seizures. A noninvasive infrared optic beam sensor (Mini mitter Inc) was then integrated single animal cages for the simultaneous recording of rest-activity periods (locomotion/behavior) and EEG. Rest-activity recordings were undertaken for 1 week, under 12 hrs of light and 12 hours of darkness after animals were having spontaneous seizures for at least 2 weeks. Mean rest-activity levels for the light (LL) and dark (LD) phases were compared between the 2 groups. Seizure data was analyzed to examine for preferential phasic occurrence of seizures during LL and LD phases.Results: Data was available for 7 epileptic and 10 control animals for analysis. As rodents are nocturnal animals, more activity was noted during the LD phase compared to LL phase for both control and epileptic animals. However, epileptic animals had significantly more activity during LL cycles (p<0.000), as well as LD cycles (p<0.05), when compared to control animals. Furthermore, subtle phase shifts were noted in the circadian rhythm of locomotion for epileptic animals. Overall, within each 24 hr period, each epileptic animal had an average of 1.11 seizures per hour during the LD and 1.01 seizures per hour during the LL. Thus no phase preference for seizures was seen for the group of epileptic animals. However subgroup analysis showed that animals with more seizure during LD appeared to have different rest activity patterns compared to rest of the animals.Conclusions: Circadian rhythm of locomotion and behavior are altered in animal models of limbic epilepsy. Epileptic animals appeared to be hyperactive both during light and dark phases of the 24 hr cycle. However no phase preference was noted for seizures in our model. Further studies are needed to definitively determine the influence of chronic epilepsy on circadian rhythm expression and much longer recordings are probably needed to detect phase shifts in circadian rhythms in this model.