A genetic form of petit mal absence in Wistar rats

One-third of the Wistar rats bred in the Centre of Neurochemistry in Strasbourg, France, develop spontaneous epileptic seizures which from their clinical manifestations, pharmacological responses, and electroencephalographic findings are suggestive of Petit Mal absences. These fits are genetically determined since in two lines selected from affected animals they occurred in 90 p. cent of three generations. The selection of a pure strain should assist in the use of this pharmacologic and neurophysiologic model of Petit Mal epilepsy.     

Spontaneous spike and wave discharges in thalamus and cortex in a rat model of genetic petit mal-like seizures

In an inbred strain of Wistar rats, spontaneous spike and wave discharges (8 to 10 c/s) appeared regularly on the EEG during quiet wakefulness and were accompanied by an arrest of behavioral activity associated with vibrissal and facial myoclonia. These seizures were recorded over the entire neocortex, but predominantly in the frontoparietal cortex. Subcortical bipolar recordings in chronic preparations showed that the lateral thalamic nuclei were greatly involved in these discharges: high-voltage spike and waves always appeared either simultaneously with, or slightly before the cortical discharges. In some cases, thalamic discharges were not accompanied by cortical discharges. No discharges were recorded in medial thalamic nuclei, in the cingulate cortex, or in the hippocampus. These results confirm the thalamocortical prevalence in the development of these rats' petit mal-like seizures, with a possible driving from thalamic nuclei.     

The connection between absence-like seizures and hypothermia induced by penicillin: possible implication on other animal models of petit mal epilepsy

In this study we investigated the relationship between penicillin-induced hypothermia and petit mal epilepsy induced by this proconvulsant antibiotic. In order to find a possible dose-dependent relationship, we used two doses: 1500.000 and 1000.000 U/kg b.wt., both known as being sufficient to induce absence-like attacks with subsequent spike and wave discharges (SWD) in electrocorticogram (ECoG). Because of experimental data suggesting penicillin binding to benzodiazepine receptor recognition site, we also studied penicillin-induced changes in body temperature after diazepam pretreatment. Results of this study clearly show that penicillin in doses known to induce petit mal-like epilepsy concomitantly induces statistically significant dose-dependent decrease in body temperature. Pretreatment with diazepam completely prevents both penicillin-induced hypothermia and SWDs. On the other hand, both the diazepam and mixed diazepam+penicillin treatments did not significantly alter body temperature. These results suggest, however, that at least some of the penicillin effects described could be assigned to its binding to the benzodiazepine receptor recognition site at GABA_A ionophore. This may have an important clinical implication because the inhibitory action of penicillin at the benzodiazepine receptor recognition site could account for the mechanism of penicillin-induced unspecific encephalopathies in humans. The relationship between petit mal epilepsy and hypothermia sheds new light on the action mechanisms of penicillin-induced absence seizures.     

Kainic acid-induced thalamic seizure in cats--a possible model of petit mal seizure.

Bipolar depth electrodes were implanted stereotaxically in the thalamus, hippocampus and midbrain reticular formation of cats. Cortical screw electrodes were placed over the bilateral sensorimotor cortex. A guide cannula with an inner injection cannula was inserted unilaterally into the posterolateral ventral nuclei (VPL) of the thalamus. Eight days after the procedures, kainic acid (2.0 micrograms) was injected unilaterally into the VPL via the injection cannula in freely moving animals and electro-clinical observations were made. About 1 h after the kainic acid injection, multiple spikes were observed in the VPL (injection site), which propagated to the subcortical structures. These seizures finally propagated bilaterally to the cortex about 2 h after the injection. About 3-4 h after the injection, small spike and wave complexes repeatedly appeared for a short period of time in cortical leads and cats exhibited behavioral arrest with unresponsiveness during the seizures. About 24 h after the injection, generalized small spike and wave complexes were observed intermittently in cortical and subcortical structures. They persisted for 4-5 s and were associated with behavioral arrest and staring. The results demonstrate that a unilateral microinjection of kainic acid into VPL induced petit mal-like seizure, and suggest that VPL plays an important role in the generation or transfer of spike and wave complexes.