Abstracts

Rationale: The relationship between circadian rhythm and epilepsy is poorly understood although circadian periodicity in the occurrence of seizures has been recognized for more than a century. Recent work by our group (Talathi et al Neurosci. Lett.,15:455, 2009; Fisher et al, Biol. Cybern., epub ahead of print 2010) has shed some light on the circadian phase dependent modulation in the excitability of hippocampus in an animal model of chronic epilepsy. In order to further elucidate the relationship between hippocampal excitability and the endogenous circadian rhythm in an epileptic brain, we have focused on systematic investigation of the alterations in the circadian activity in relation to spontaneous seizures in an animal model of chronic epilepsy. Here we report preliminary findings of the changes in the circadian rhythm of the core body temperature (CBT) in an animal model of chronic epilepsy. Methods: Male Sprague-Dawley rats (n=2) weighing ~265 g were implanted with an RF transponder in the abdominal cavity and a stimulating electrode in the ventral hippocampus. Following recovery the rats were transferred to controlled 24 h LD environment. The CBT was continuously monitored. After baseline recordings, the rats were brain injured through electrical stimulation. The CBT rhythm of rats with injured brains was monitored for 4 weeks in 24 h LD cycle. During this time period the rats exhibited spontaneous seizures. The rats were then moved to 24 DD (constant routine) environment and monitored for four additional weeks. The Lomb Scargle periodogram was used to estimate the period of statistically significant oscillations in the circadian range. Results: Following injury, after a transient period of 4-5 days, the mean CBT rose by 0.23 0.07 oC and the period of circadian rhythm decreased by 0.3 0.01 h. The phase of CBT oscillation shifted by -1.38 0.003 h. After the rats were transfered to 24 DD routine, the mean CBT returned to baseline, however the CBT free-ran with endogenous period of 24.46 0.007 h. The phase was observed to be shifted to 0.95 0.6 h. In addition a statistically significant peak (p<0.05) at ~12 h was observed in the Lomb Scargle periodogram. The occurrence of spontaneous seizures did not have any observable effect on the rhythm of CBT. Conclusions: Brain injury transiently disturbs the circadian rhythm of CBT and the rhythm appears to be desynchronized from the LD cycle with period less than the imposed 24 h period. In addition, statistically significant peak in CBT rhythm at ~12 h is observed in epileptic rats under constant routine protocol. We hypothesize that ~12 h harmonic in the periodogram of CBT rhythm, which is unmasked in the constant routine protocol, is induced by seizures. This harmonic in turn shifts the phase of the CBT rhythm, and in turn may be associated with hyperexcitability observed in an epileptic brain