Amino acid content of the brain in rats focal penicillin induced epilepsy.

The initial objective of the present study was to investigate the role of excitatory and inhibitory amino acids in generalized as compared to focal epilepsy, both forms being induced by the same convulsant agent, i.e. penicillin. Our attempts to obtain in the rat the generalized epilepsy, constantly induced in cats by systemic administration of penicillin, were unsuccessful. This is probably due to the rudimentary development of the cerebral cortex in rodents as compared to the feline cortex. The tentative conclusion was drawn that the cortex is the brain structure mainly involved in the genesis of petit mal seizures. Penicillin was applied to the cortex of 40 white Wistar rats and the electrical cortical activity was registered. The concentrations of glutamate, aspartate, glycine, GABA and serine were determined in the cerebral cortex, the brain stem and the cerebellum. The same amino acids were determined in the brain of 20 controls. No significant changes in the amino acid contents were obtained in the cerebral cortex. In the brain stem the glutamate level was significantly increased while the glycine content was markedly decreased. These findings are consistent with the involvement of the brain stem structures in seizure activity.

Increased susceptibility to audiogenic seizures following withdrawal of progesterone.

This investigation was performed to verify a previous hypothesis which correlates the catamenial seizures with the stoppage of progesterone secretion. White rats from a Wistar strain were tested with an electric bell. Thirty-five animals refractory to the acoustic stimulus were selected for the experiment. Each animal received 9 daily injections with progesterone, 5 mgr/day. The animals were tested with the acoustic stimulus after the 5th and the 9th injections, 24 hours after the administration of the last dose. Audiogenic seizures were obtained in 29.4% of the rats tested after 5 injections and in 40.0% of the rats tested after the 9th injection. The increased seizure susceptibility lasted 3-8 days after the hormone withdrawal. In conclusion, the withdrawal of high doses of progesterone exerts a seizure-activating effect.

The cerebral content of excitatory and inhibitory amino acids in rats following withdrawal of antiepileptic drugs.

The aim of the present study was to investigate the role of amino acids in the increased seizure susceptibility induced by withdrawal of antiepileptic drugs (AEDs). Fifty white Wistar rats treated with AEDs and 30 controls were used. The animals were previously exposed to the acoustic stimulus and only the non responsive were used. The administered AEDs were morphosuximide, ethosuximide, phenobarbital, valproate and gluthetimide. The treatment was discontinued after 2 weeks. The acoustic stimulation was repeated after 2-4 days of abstention. The animals were sacrificed and the amino acids glutamate, aspartate, GABA, glycine and serine were determined in the cortex and the brain stem. The withdrawal of AEDs induced seizure susceptibility in 71% of the rats treated with phenobarbital and in 76% of those receiving morphosuximide. A significant increase of glutamate levels was found in the brain stem following withdrawal of both morphosuximide and ethosuximide. The level of GABA was elevated in the brain stem after valproate and morphosuximide withdrawal. The increase of glutamate concentration can be correlated with the increased seizure susceptibility. The unexpected rise of the GABA level could be interpreted as a compensatory inhibitory mechanism.

Lidocaine kindling does not generate epilepsy.

Forty Wistar rats were injected with a solution of lidocaine (90 mg/kg s.c.) 5 days per week for 30-40 days. In 36 of the animals, attacks of stiffness were obtained. After a period of disordered movements, the animals, remained completely immobile with the hindlimbs rigidly extended. The attacks of stiffness lasted from 10 to 60 minutes. The hemisection of the spinal cord at the thoracic level suppressed the rigidity of the ipsilateral leg. Electrical recording with electrodes applied to the cortex or implanted in the depth of the temporal lobe failed to reveal paroxysmal activity. These data could not confirm the results of other authors reporting typical epileptic seizures after lidocaine kindling. Despite essential differences, epileptic kindling and lidocaine-kindled stiffness attacks are both manifestations of the central nervous system plasticity. Therefore it appears that pharmacologically induced plasticity is a more general process than epileptic kindling.

Brain amino acid levels in audiogenic seizure-susceptible rats following habituation to the auditory stimulus.

Hippocampic and brain stem levels of amino acids were determined in audiogenic seizure-susceptible rats following habituation by repeated exposure to the acoustic stimulus. The biochemical determinations were performed in the brains of 42 habituated animals and 23 not habituated seizure susceptible rats used as controls. It was found that the habituation process is associated with: a) increased levels of aspartate in hippocampus and pons; b) significantly decreased levels of glycine in the hippocampus and pons; c) decreased concentration of glutamate in the pons; d) no significant changes in the GABA concentrations in hippocampus and brain stem. The changes of the excitatory and inhibitory amino acids in the brain of the habituated rats cannot explain the fall in epileptic susceptibility associated with habituation.