Does Seizure Activity Produce Purkinje Cell Loss?

Abstract

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.

Cerebellar white matter changes in patients with newly diagnosed partial epilepsy of unknown etiology

“…Several hypotheses about the mechanism of volume reduction in the cerebellum have been postulated. These include seizure-induced damage (e.g., hypoxia), the effects of AEDs (e.g., phenytoin), and the potential effects of initial etiological insults and early neurodevelopmental factors [10,28,29]. However, the studies that include patients with CHE did not show a causal relationship between the pre-existing anatomic abnormalities in the cerebellum with the onset of epilepsy.…”

Unaltered neuronal and glial counts in animal models of magnetic seizure therapy and electroconvulsive therapy

“…Quantitative studies of unmodified ECS in rats found no effects on neuronal number in neocortex (Colon and Notermans, 1975), hippocampus (Dam et al, 1980; Gombos et al, 1999; Laursen et al, 1991), cerebellum (Dam et al, 1984), or thalamus (Laursen et al, 1991; Vaidya et al, 1999). In the only stereological study to include hippocampal granular cell neurons, these were greater in number, and the granular cell layer and hilus were greater in volume, in rats receiving daily unmodified ECS for 10 days, compared with rats receiving sham treatments; CA1 and CA2–3 were unaffected (Chen et al, 2009).…”

Accumulation of nuclear DNA damage or neuron loss: Molecular basis for a new approach to understanding selective neuronal vulnerability in neurodegenerative diseases

“…Furthermore, the cerebellar Purkinje cells displayed the highest relative amount of nDNA SSB of all investigated cell types (in young animals approximately three times more than the hippocampal pyramidal cells; [10]) although the relative amount of nDNA repair was comparable among Purkinje cells and hippocampal pyramidal cells [20]. The high relative amount of nDNA SSB observed in Purkinje cells was most probably due to the fact that these cells are among the largest neurons in the CNS and have an exceptionally high metabolic demand [89][90][91]. On the other hand, this high metabolic demand has also been hypothesized to be involved in the high vulnerability of Purkinje cells under conditions such as acute hypoxia or seizures [89][90][91].…”

“…The high relative amount of nDNA SSB observed in Purkinje cells was most probably due to the fact that these cells are among the largest neurons in the CNS and have an exceptionally high metabolic demand [89][90][91]. On the other hand, this high metabolic demand has also been hypothesized to be involved in the high vulnerability of Purkinje cells under conditions such as acute hypoxia or seizures [89][90][91]. Based on these data we have hypothesized that the lack of age-related increase in the relative amount of nDNA SSB in Purkinje cells does not reflect an exception from Gensler and Bernstein's [86] hypothesis but rather indicates a fundamental difference in the selective neuronal vulnerability of Purkinje cells during aging compared to the other types of neurons mentioned above.…”