Abstracts

Seizures in both humans and animals are often associated with significant alterations in body temperature. These alterations may influence degenerative processes within the brain. We tested the hypothesis that alterations in body temperature affect neurodegeneration in commonly used animal models of seizures and status epilepticus. Adult male rats (n =38) weighing between 350-450 grams were used as subjects. The four seizure models used were pentylenetetrazol (PTZ, 40mg/kg i.p.), pilocarpine (PILO, 350mg/kg i.p.), kainic acid (KA, 15mg/kg i.p.), and sustained amygdala stimulation (SAS, 30min electrical stimulation of the left basolateral amygdala). Animals were randomly assigned to the 4 different seizure groups (n = 8/group) and one control (n = 6). Five animals from each group were equipped with body temperature recording devices (SubCue[trade], Calgary Ab Canada). SAS animals had bipolar stimulating/recording electrodes placed bilaterally in the basolateral amygdalae. Body temperature, in all groups, was recorded at 5 min intervals. In addition the SAS group had EEG recorded before, during, and after seizure induction. Twenty-four hours later animals were sacrificed and processed for Fluoro-Jade histochemistry, as a means to identify degenerating neurons. Neurodegeneration was assessed by a trained observer, blinded to experimental conditions. All models were associated with significant changes in body temperature after seizure induction. Robust hypothermic responses were observed in the PTZ (low = - 1.55 [plusmn] 0.11 [deg]C, mean [plusmn] SEM compared to baseline p [lt] 0.05) and PILO (low = - 3.39 [plusmn] 0.42 [deg]C, p [lt] 0.01). The KA group showed a predominately hyperthermic response (max = + 1.17 [plusmn] 0.43 [deg]C, p [lt] 0.05), the SAS group also showed a significant hyperthermic component (max = + 1.67 [plusmn] 0.36 [deg]C, p [lt] 0.05). After 24 hrs neurodegeneration was greatest in the KA group and SAS groups compared to PILO, PTZ, and saline treated animals. These changes were confined to limbic regions including the basolateral and central amygdaloid nuclei, piriform cortex, and mediodorsal thalamus (KA group p [lt] 0.05, ANOVA, LSD post hoc compared to PILO, PTZ and Saline). In addition the SAS group had significantly more damage in the central amygdala compared to the PILO group (p [lt] 0.05, ANOVA, LSD post hoc). We conclude that increases in body temperature are associated with differences in neurodegeneration between seizure models. Minimizing these changes could eliminate some of the variations observed between models. (Supported by Canadian Institutes of Health Research.)