Experimental Cobalt Epilepsy and the Cerebellum

Dow, Robert S.

doi:10.1007/978-1-4613-4508-4_4

Cited by 7 publications

(5 citation statements)

References 38 publications

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“…This inhibition may be important, helping to maintain neuronal excitability below the seizure threshold. It has thus been shown that total cerebellar removal increases the lifetime of an acute penicillin microfocus in the cerebral cortex (Gartside, 1978) and enhances seizures from a cobalt focus in rats (Dow et al, 1962;Dow, 1974). Similarly, it was found that Purkinje cells and inhibitory interneurons fire either a single spike or a short burst of spikes after cortical epileptiform spike (Gartside, 1979).…”

Section: Discussionmentioning

confidence: 98%

Does Seizure Activity Produce Purkinje Cell Loss?

et al. 1984

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Eight Wistar rats were exposed to 140 electroconvulsive seizures over 50 days. Ten rats served as controls. The density of Purkinje cells in cerebellum ranged from 15.3 to 18.5/mm in the treated rats and from 15.2 to 19.1/mm in the controls. No Purkinje cell loss was disclosed in the rats subjected to electroconvulsive seizures. Twenty-five Mongolian gerbils of the seizure-susceptible strain were selected according to seizure score with five animals in each group. Five Mongolian gerbils of a seizure-resistant strain served as controls. The density of the Purkinje cells ranged from 21.4 to 29.8/mm in the seizure-susceptible animals and from 27.6 to 31.5/mm in the controls, with a lower density in the gerbils with seizures compared with the controls (p less than 0.05). There was no relation to type or number of seizures. Eight gerbils of the seizure-susceptible strain were included as a supplementary group, to disclose any possible genetic trait as an explanation of the lower Purkinje cell density. The Purkinje cell density in these animals ranged from 24.8 to 30.9/mm and did not differ from the density in the seizure-resistant gerbils. Thus the lower density of Purkinje cells in the seizure-susceptible Mongolian gerbils is a result of seizure activity. The excessive epileptic input with stimulation of the glutamatergic innervation of the Purkinje cells resulting in a persistent elevated gamma-aminobutyric acid (GABA) tone may explain the damage to the Purkinje cells in the gerbils and the loss of Purkinje cells found in patients with severe epilepsy.

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Section: Discussionmentioning

confidence: 98%

Does Seizure Activity Produce Purkinje Cell Loss?

et al. 1984

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“…seizure suppression have not been clearly defined. Cerebellar involvement in seizure suppression is suggested by the effects of cerebellar stimulation and ablation on induced focal cortical epilepsy in experimental animals (Cooke and Snider, 1955;Steriade, 1960;Dow et al, 1962;Reimer et al, 1962;Mutani et al, 1969;Hutton et al, 1976;Julien and Halpern, 1972; Babb et al, 1974;Dow, 1974;Hablitz et al, 1975), and cerebellar stimulation has recently been introduced as a treatment for intractable epilepsy in man (Cooper et al, 1974(Cooper et al, , 1978, although the efficacy of the procedure remains controversial.…”

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confidence: 99%

Combined Study of the Pattern of Spontaneous Activity of Cerebellar Purkinje Cells and Phenytoin Serum Levels in the Rat

Latham

Paul

1980

Epilepsia

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The effects of phenytoin (PHT) on the spontaneous activity of cerebellar Purkinje cells and the drug serum levels have been examined following both intravenous and intraperitoneal administration in rats. Purkinje cell activity was assessed by on-line computer analysis of interspike interval distributions. PHT levels were assayed in blood samples taken at the end of the electrophysiological experiments and in successive samples obtained in parallel experiments over periods corresponding to when electrophysiological recordings were made. Single intravenous doses of PHT (10 mg/kg) produced a decrease in the discharge rate in individual Purkinje cells with a time course which was delayed and prolonged compared with the changes in serum levels of PHT. A single intraperitoneal dose of PHt (100 mg/kg) produced a statistically significant (p < 0.02) decrease in Purkinje cell discharge rate. Similar results (p < 0.01) were obtained after pretreatment with PHT (50 mg/kg daily for 14 days, including the day of the experiment). Both injection schedules produced nontoxic serum PHT levels during the recording period. Pretreatment with PHT doses of 10 mg/kg for 14 days (including the experimental day) produced a smaller decrease in Purkinje cell discharge rate (p < 0.05). When pretreatment ceased the day before the electrophysiological experiment, no significant changes in Purkinje cell activity were observed, and serum PHT levels were not detectable at the end of the experiment. None of the pretreatment schedules produced overt signs of cerebellar dysfunction or motor impairment. These findings indicate that PHT may increase the output from the cerebellum by suppressing Purkinje cell activity. Since this effect occurs without producing cerebellar symptoms, it may account for some of the therapeutic action of PHT at nontoxic levels in man.

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“…Our results in monkeys indicate that although interictal EEG bursting does decrease with cerebellar stimulation, seizure frequency increases during and especially following weeks of stimulation. In fact, when cerebellar stimulation has been efficacious in other animal models, its influence has been most obviously manifested on EEG concomitants of epilepsy other than ictal events (Boone et al, 1974;Dow, 1974;Meyers and Bickford, 1974;Soper et al, 1977). Either minimal effects to no changes (Black et al, 1976;Babb et al, 1977;Strain et al, 1977) or an increase in frequency (Bantli et al, 1978) has been reported for animals with overt seizures.…”

Section: Discussionmentioning

confidence: 99%

“…Following a demonstration of a decrease in seizures in several acute animal models of epilepsy (reviewed by Dow, 1974) with electrical stimulation of the surface of the anterior vermis of the cerebellum, Cooper et al (1973) reported a reduction in seizure frequency with similar stimulation in man. More recently, Cooper et al (1976) reported the effects of cerebellar stimulation in 15 cases followed for 11 months or longer: 3 of 6 patients with psychomotor seizures, 4 of 6 patients with primarily generalized convulsive seizures, and all 3 patients with myoclonus were either markedly improved or seizure free.…”

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confidence: 99%

Cerebellar Stimulation in Alumina‐Gel Monkey Model: Inverse Relationship Between Clinical Seizures and EEG Interictal Bursts

et al. 1979

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The efficacy of cerebellar stimulation was addressed in a chronic monkey model (N = 12) of spontaneous focal motor and secondarily generalized seizures using 24 hr seizure frequency monitoring and all-night EEG recording. The anterior cerebellar vermis was stimulated employing parameters similar to those used in man, 10 Hz, 1 msec pulses, 10 min on, 10 off, at an average current of 2.0 mA. Six weeks pre- and post-base-line periods were compared to a stimulation period of the same length. The results contribute to a clarification of conflicting findings of previous researchers by revealing an inverse relationship between seizure frequency and interictal EEG bursts during the weeks of stimulation. Seizure frequency increased significantly and interictal bursts decreased. Both of these effects (especially the former) were evident in the post-stimulation period, but for different reasons than hypothesized for the period of stimulation. Whereas the therapeutic value of cerebellar stimulation on seizures may be in question, its utilization in the study of mechanisms of epilepsy may be warranted.

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Experimental Cobalt Epilepsy and the Cerebellum

Cited by 7 publications

References 38 publications

Does Seizure Activity Produce Purkinje Cell Loss?

Does Seizure Activity Produce Purkinje Cell Loss?

Combined Study of the Pattern of Spontaneous Activity of Cerebellar Purkinje Cells and Phenytoin Serum Levels in the Rat

Cerebellar Stimulation in Alumina‐Gel Monkey Model: Inverse Relationship Between Clinical Seizures and EEG Interictal Bursts

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