Effects of Acute and Chronic Paleocerebellar Stimulation on Experimental Models of Epilepsy in the Cat: Studies with Enflurane, Pentylenetetrazol, Penicillin, and Chloralose

Effects of acute and chronic paleocerebellar stimulation were evaluated in four experimental models of epilepsy in 24 adult cats chronically implanted with bilaterally symmetric parasagittal electrocorticographic electrodes and anterior lobe cerebellar stimulation electrodes. Pentylenetetrazol was given intraveneously in 50-mg increments or 4% enflurane was inspired until grand mal seizures occurred spontaneously or were triggered by photic or auditory stimuli. Alpha-chloralose, 50 mg/kg, was injected intraperitoneally to produce a model of stimulus-sensitive myoclonus and sodium penicillin G, 350,000 units/kg, was injected intramuscularly to produce a model of petit mal epilepsy. One- to 250-Hz electrical stimulation of paleocerebellar cortical surfaces was performed with constant-voltage or constant-current stimulators at threshold and suprathreshold intensities with average intensities of 8 V and 2.5 mA, respectively. Acute or chronic, threshold or suprathreshold paleocerebellar stimulation did not predictably alter the electrographic or clinical manifestations in any of these four models.     

Effects of topiramate on oral dyskinesia induced by reserpine

Recently, we have described the antidyskinetic property of the GABA mimetic drug valproic acid on reserpine-induced oral dyskinesia, an animal model that has been related to tardive as well as acute dyskinesias, which are associated with important neuropathologies. The present study investigates the effects of different doses of the GABA mimetic anticonvulsant topiramate on the manifestation of reserpine-induced orofacial dyskinesia. Female EPM-M1 mice received two injections of control solution or of 0.5 mg/kg reserpine separated by 48 h. Twenty-four hours after the second reserpine or control solution injection, animals were acutely treated with control solution or topiramate (1, 3, 10 or 30 mg/kg) and were observed for quantification of oral dyskinesia or general activity in an open-field. In order to verify the effects of topiramate per se on oral dyskinesia or general activity, female EPM-M1 mice were acutely treated with control solution or 1, 3, 10 or 30 mg/kg topiramate and observed for quantification of oral dyskinesia and general activity. The highest dose of topiramate completely abolished the manifestation of reserpine-induced oral dyskinesia whereas the doses of 3 and 10 mg/kg significantly attenuated it. None of the doses of the anticonvulsant modified spontaneous locomotion frequency or oral movements, whereas spontaneous rearing frequency was decreased by 3, 10 and 30 mg/kg topiramate. The highest dose of topiramate did not modify general activity in reserpine-treated mice. These results support the potential therapeutic use of topiramate in the treatment of oral dyskinesias.     

Experimental Bilateral Deep Temporal Epilepsy. Effects of Ablation of One Focus and of Different Brain Lesions

In acute experiments in the rabbit, the amygdaloid nuclear complexes of the two sides were made epileptogenic through electrical stimulation or local injection of penicillin in gel. The effects on the epileptic pattern produced by surgical removal of one of the two epileptogenic amygdalae and the effects of sterotactic lesioning of the region of anterior commissure, head of caudate nucleus, and occipital cortex were analyzed. The occurrence of phenomena of both inhibitory and facilitatory interaction between the two epileptogenic amydalae was confirmed. In some experimental conditions, the restraining influence of an amygdaloid penicillin focus on the contralateral one was quite relevant, and its effect could persist even after surgical removal of the focus from which it originated. The mediation of the interamygdadoid epileptic interaction could not be ascribed to a single cerebral structure or anatomofunctionally homogenous group of structures. The phenomenon appears to involve several structures at different encephalic levels.     

Anticonvulsant Drugs Selectively Affect Kindled and Penicillin Epilepsy, Especially During Seizure-Prone Sleep or Awakening States in Cats

Carbamazepine (CBZ) selectively suppressed kindled convulsions, whereas ethosuximide (ESM) suppressed spike-wave activity accompanying systemic penicillin epilepsy in cats. Evoked potential data indicated that CBZ acted at the thalamic level, whereas ESM acted at cortex. Reduction of seizures and thalamic or cortical excitability occurred throughout the sleep-wake cycle, but effects were most pronounced in seizure-prone sleep or awakening states. These findings extend previous work showing differential antiepileptic drug (AED) effects on temporal lobe and absence seizures. The results are also consistent with recent work suggesting that thalamocortical pathways provide a final common pathway for the manifestation of sleep and awakening epilepsy and also reflect a chronic, latent pathophysiology.