Limbic Self‐sustaining Status Epilepticus in Rats Is Not Associated with Hyperthermia

Abstract

Summary: Purpose:To evaluate the impact of limbic status epilepticus on temperature.Methods: The perforant path in freely moving rats was stimulated electrically for 120 min to induce self-sustaining status epilepticus (SSSE). For 150 min after the end of stimulation, epidural temperature and electrographic and clinical seizure activity were assessed in animals with limbic and motor SSSE, as well as in animals without development of SE.Results: Temperature in all animals with SSSE was elevated by 1.5 ± 0.8• C after the end of stimulation compared with baseline values (p < 0.01). In animals with pure limbic SE, temperature decreased continuously to baseline values over the 150-min period of observation. In contrast, in animals with motor SSSE, temperature remained elevated during continuing epileptic activity and was still significantly higher 150 min after the end of stimulation compared with baseline (p < 0.01). In animals that did not develop SSSE, temperature was not changed after the end of electrical stimulation and in the 150 min thereafter compared with baseline values. Conclusions:The results indicate that hyperthermia as seen in SE is the consequence of motor convulsions and not of epileptic activity itself, as seen in limbic SSSE.

Inflammatory markers associated with seizures

“…Hyperthermia is caused by exogenous heat exposure or endogenous heat production (Dinarello and Porat, ). In animals with limbic self‐sustained status epilepticus, a significant elevation in BT developed only in those with motor convulsions, which suggested that hyperthermia was the consequence of motor convulsions and not of epileptic activity itself (Schmitt et al ., ). However, as a few patients with complex partial status epilepticus were reported to exhibit elevated BT as an ictal phenomenon, thermoregulatory neurons in hypothalamus may be affected by circumscribed propagation of epileptic activity (Semel, ; el‐Ad and Neufeld, ).…”

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“…This allows confirmation of the health status of the animals and helps to avoid the use of animals whose body temperature is not in the physiologic range. As an example, the induction of SE by pilocarpine leads in animals to high fever, and monitoring seizure‐induced changes could help our understanding of why animals do or do not survive the SE phase, and whether mortality might be, at least in part, related to temperature elevation …”

“…Moreover, failure to measure body temperature can confound the interpretation of experiments, as it may not be known whether, for example, extreme change in body temperature contributed to an outcome, or whether an intervention (e.g., an anti‐inflammatory agent) had an indirect impact by changing body temperature, rather by another mechanism of action. In experimental epilepsy models, body temperature increases during SE . Furthermore, the circadian rhythm of temperature is altered in epileptic rats, which is associated with regional hypothalamic neuronal loss .…”

“…As an example, the induction of SE by pilocarpine leads in animals to high fever, and monitoring seizure-induced changes could help our understanding of why animals do or do not survive the SE phase, and whether mortality might be, at least in part, related to temperature elevation. 17 Febrile seizures are common in young children aged 6 months to 6 years. 18 Most febrile seizures are benign, but complex, prolonged febrile seizures lasting over 10-20 minutes are associated with a risk of developing subsequent epilepsy.…”

“…In experimental epilepsy models, body temperature increases during SE. 17 Furthermore, the circadian rhythm of temperature is altered in epileptic rats, which is associated with regional hypothalamic neuronal loss. 21 Rats that were cooled during SE had a significantly lower body temperature compared to cooled control rats or non-SE rats, 22 indicating a disturbed temperature homeostasis during SE.…”