Barbara Barna

Chronic low-dose maternal exposure to methylmercury enhances epileptogenicity in developing rats

Effects of continuous low‐dose maternal methylmercury intoxication on the induction and propagation of ictal epileptiform activity induced by 3‐aminopyridine, were investigated on the neocortex of 4‐weeks‐old offspring rats. Epileptogenicity was significantly increased in offspring of mercury‐treated animals compared to those of controls, characterized by more frequent occurrence of periodic ictal activity, a facilitated propagation of epileptiform discharges and a strong tendency to generalization. The latency of first ictal event was slightly shorter and the average duration of individual ictal periods slightly longer in treated animals. However, the amplitude of seizure discharges was significantly smaller in treated animals than in controls.

Effect of a glutamate receptor antagonist (GYKI 52466) on 4-aminopyridine-induced seizure activity developed in rat cortical slices

In the present experiments we have tested the effect of the noncompetitive AMPA antagonist GYKI 52466 (20-80 microM) on spontaneous epileptic discharges developed as the consequence of 4-aminopyridine application in neocortex slices of adult rats. Parallel to the changes of spontaneous activity, the field potentials, evoked by electrical stimulation of the corpus callosum, were also analyzed. Glass microcapillary extracellular recording electrode was positioned in the third layer of the somatosensory cortex slice, while the stimulating electrode was placed at the border of the white and gray matter. 4-aminopyridine and GYKI 52466 were bath-applied. The application of 40 microM GYKI 52466 caused about 40% decrease in the frequency and the amplitude of spontaneous seizures as well as the duration of each discharges developed in 4-amino-pyridine. Pre-incubation with the AMPA antagonist effectively inhibited both the development of seizure activity and the maintenance of the discharges. GYKI 52466 also decreased the duration and amplitude of field responses evoked by stimulation of the corpus callosum. This inhibitory effect was dose-dependent. Our data in the in vitro cortex slice epilepsy model suggest that the non-competitive AMPA antagonist GYKI 52466 is a potent anticonvulsant and neuroprotective compound because it reduced the fully developed epileptic discharges or prevented their development.

Effects of continuous low-dose exposure to organic and inorganic mercury during development on epileptogenicity in rats.

The effects of chronic, low-dose fetal and lactational organic (MeHgCl) and inorganic (HgCl2) mercury intoxication on epileptogenicity were investigated and compared in rats. The main observations after both mercury treatments were a facilitated seizure expression and propagation evoked by 4-aminopyridine (4-AP). The seizure susceptibility of the offspring seemed to be in a parallel relation to the mercury concentration in the cortical tissue, which was significantly higher in treated animals as compared to the controls. While MeHgCl enhanced the number of ictal periods, HgCl2 facilitated the duration of seizure discharges in younger animals. HgCl2 intoxication seemed to be more permanent than MeHgCl. Changes in the summated ictal activity--which is an indication of epileptogenicity--were observed in the opposite directions in the two treated groups with increasing age. The amplitudes of seizure discharges were smaller in both mercury-treated groups than in the controls, which could be a consequence of a depressed proliferation of neurons or enhanced cell death in the neocortex. In summary, we observed that adult rats exposed to organic or inorganic mercury chemicals during their embryonic life, are more prone to epilepsy than control rats given only 4-AP.

Anticonvulsive effect of AMPA receptor antagonist GYKI 52466 on 4-aminopyridine-induced cortical ictal activity in rat

The effect of GYKI-52466 (1-(4-aminophenyl)-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine), a selective antagonist of AMPA receptor was investigated on the generation and manifestation of 4-aminopyridine-induced cortical epileptiform activity. In vivo experiments were carried out on pentobarbital-anaesthetised adult rats. Ictal epileptiform activity was induced by local application of 4-aminopyridine (4-Ap) to the surface of somatosensory cortex. In one group of animals, GYKI 52466 was administered intraperitoneally before 4-Ap application, in another group, the already active primary focus was treated locally by GYKI 52466. Different parameters of epileptic activity were measured and compared in GYKI 52466-treated and control animals. The results demonstrate that GYKI 52466 exerts anticonvulsive effects on both the induction and the expression of epileptiform activity, by delaying the onset of the first ictal event, decreasing the numbers and duration of ictal periods, as well as the amplitudes of epileptiform discharges both in the primary and mirror foci. However, seizure propagation to other cortical areas seemed to be facilitated. The anticonvulsive effect of GYKI 52466 was stronger in pretreatment than in treatment of ongoing epileptiform activity. As a conclusion, it is supposed that AMPA receptors are probably more dominant in the induction of epileptiform activity than in the maintenance of it, mainly through the activation of corticothalamo-cortical networks. It is also supposed that the cortical inhibition which blocks the propagation of epileptiform process might be activated mainly through non-N-methyl-D-aspartate receptors.

Slow dynamics of epileptic seizure: Analysis and model ☆

Abstract The slow dynamics of epileptic seizures are studied by combining in vivo electrophysiology, data analysis by using wavelet transformation and neural network modeling. Even a skeleton model with simple neurodynamics was able to reproduce many characteristics of the epileptic seizure.