In the current study the link among the γ-hydroxybutyrate (GHB)/
pentylenetetrazole (PTZ)-induced absence-like
seizures and concomitant decreases in the core temperature, as well as electroencephalographic (EEG) activity during
rewarming from deep
hypothermia produced by a
drug-free protocol were investigated. During the
rewarming period after deep cooling, most Wistar rats suffered from bilaterally synchronous spike and waves with no or mild behavioral correlates. Spike and wave
seizures were temperature-dependent and were initially registered when body temperature (Tb) reached 25-27°C, but mostly during the mild
hypothermia of 0.3-1.3°C (Tb of 36.3-37.3°C). In chemical absence models, spike and wave discharges were also closely accompanied by mild systemic
hypothermia, as both PTZ- and GHB-induced temperature decreases ranged from about 1-1.4°C respectively, together with EEG markers of absence activity. Thus, throughout the different experimental designs, the occurrence of spike and wave discharges was always related to a mild (0.3-1.4°C) decrease of Tb.
Benzodiazepine diazepam as the GABAA-positive allosteric modulator and
CGP 62349 as the selective antagonist of GABAB receptors were used to determine if their well-known
anticonvulsant properties also affect
hypothermia elicited by these drugs. Finally, during the course of spontaneous
rewarming from deep
hypothermia, another selective GABAB-blocking agent,
CGP 35348, was used to elucidate if GABAB inhibitory system could be critically implicated in the generation of
hypothermia-dependent spike and waves.
Diazepam prevented both the PTZ-
induced hypothermia and electrographic absence
seizures, but these two beneficial effects did not occur in the GHB model. Even though
diazepam delayed GHB-induced maximal temperature decrease, the GHB effects remained highly significant. The GABAB antagonist
CGP 62349 completely prevented
hypothermia as well as absence
seizures in both chemical models. Likewise, spike and wave discharges, registered during the spontaneous
rewarming from deep
hypothermia, were completely prevented by
CGP 35348. These findings show that systemic
hypothermia should definitely be regarded as a marker of GABAB receptor activation. Moreover, the results of this study clearly show that initial mild temperature decrease should be considered as strong absence-provoking factor.
Hypothermia-induced nonconvulsive
seizures also highlight the importance of continuous EEG monitoring in children undergoing
therapeutic hypothermia after
cardiac arrest. Since every change in peripheral or systemic temperature ultimately must be perceived by preoptic region of the anterior hypothalamus as the primary thermoregulatory and sleep-inducing center, the preoptic thermosensitive neurons in general and warm-sensitive neurons in particular, simply have to be regarded as the most probable candidate for connected thermoregulatory and absence generating mechanisms. Therefore, additional studies are needed to confirm their potential role in the generation and propagation of absence
seizures.