Starting from simple clinical statistics, the spectrum of methods used in epilepsy research in the Institute of Physiology of the Czechoslovak (now Czech) Academy of Sciences progressively increased. Professor Servít used electrophysiological methods for study of brain activity in lower vertebrates, neuropathology was focused on electronmicroscopic study of cortical epileptic focus and ion-sensitive microelectrodes were used for studies of cortical direct current potentials. Developmental studies used electrophysiological methods (activity and projection of cortical epileptic foci, EEG under the influence of convulsant drugs, hippocampal, thalamic and cortical electrical stimulation for induction of epileptic afterdischarges and postictal period). Extensive pharmacological studies used seizures elicited by convulsant drugs (at first pentylenetetrazol but also other GABA antagonists as well as agonists of glutamate receptors). Motor performance and behavior were also studied during brain maturation. The last but not least molecular biology was included into the spectrum of methods. Many original data were published making a background of position of our laboratory in the first line of laboratories interested in brain development.

• MeSH
• Academies and Institutes MeSH
• Biomedical Research trends   MeSH
• History, 20th Century MeSH
• History, 21st Century MeSH
• Epilepsy * physiopathology   MeSH
• Humans MeSH
• Brain drug effects   physiology   growth & development   MeSH
• Animals MeSH
• Check Tag
• History, 20th Century MeSH
• History, 21st Century MeSH
• Humans MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Historical Article MeSH
• Review MeSH
• Geographicals
• Czech Republic MeSH

Background: Postictal refractoriness, i.e., the inability to elicit a new epileptic seizure immediately after the first one, is present in mature animals. Immature rats did not exhibit this refractoriness, and it is replaced by postictal potentiation. In addition to the immediate postictal potentiation, there is a delayed potentiation present at both ages. These phenomena were studied using cortical epileptic afterdischarges as a model. Objective: We aimed to analyze participation of adenosine A1 receptors in postictal potentiation and depression. Methods: Adenosine A1 receptors were studied by means of Western blotting in the cerebral cortex with a focus on the age groups studied electrophysiologically. Stimulation and recording electrodes were implanted epidurally in 12- and 25-day-old rats. The first stimulation always induced conditioning epileptic afterdischarge (AD), and 1 min after its end, the stimulation was repeated to elicit the second, testing AD. Then, the drugs were administered and paired stimulations were repeated 10 min later. A selective agonist CCPA (0.5 and 1 mg/kg i.p.) and a selective antagonist DPCPX (0.1, 0.5 and 1 mg/kg i.p.) were used to examine the possible participation of adenosine A1 receptors. Results: Control younger animals exhibited potentiation of the testing AD and a moderate increase in both conditioning and testing ADs after an injection of saline. The A1 receptor agonist CCPA shortened both post-drug ADs, and neither potentiation was present. The administration of an antagonist DPCPX resulted in marked prolongation of the conditioning AD (delayed potentiation), and the second testing AD was shorter than the post-drug conditioning AD, i.e., there was no longer immediate potentiation of ADs. To eliminate effects of the solvent dimethylsulfoxide, we added experiments with DPCPX suspended with the help of Tween 80. The results were similar, only the prolongation of ADs was not as large, and the testing ADs were significantly depressed. The older control group exhibited a nearly complete suppression of the first testing AD. There was no significant change in the conditioning and testing ADs after CCPA (delayed potentiation was blocked). Both groups of DPCPX-treated rats (with DMSO or Tween) exhibited significant augmentation of delayed potentiation but no significant difference in the immediate depression. Adenosine A1 receptors were present in the cerebral cortex of both age groups, and their quantity was higher in 12- than in 25-day-old animals. Conclusions: An agonist of the A1 receptor CCPA suppressed both types of postictal potentiation in 12-day-old rats, whereas the A1 antagonist DPCPX suppressed immediate potentiation but markedly augmented the delayed one. Immediate postictal refractoriness in 25-day-old rats was only moderately (non-significantly) affected; meanwhile, the delayed potentiation was strongly augmented.

• Keywords
• adenosine receptors, cerebral cortex, electrical stimulation, epileptic afterdischarges, ontogeny, postictal period, rat,
• Publication type
• Journal Article MeSH

The GluN2A subunit of N-methyl-D-aspartate (NMDA) receptors becomes dominant during postnatal development, overgrowing the originally dominant GluN2B subunit. The aim of our study was to show changes of anticonvulsant action of the GluN2A subunit-preferring antagonist during postnatal development of rats. Possible anticonvulsant action of GluN2A-preferring antagonist of NMDA receptors P = [[[(1S)-1-(4-bromophenyl)ethyl]amino](1,2,3,4-tetrahydro-2,3-dioxo-5-quinoxalinyl)methyl]phosphonic acid tetrasodium salt (PEAQX) (5, 10, 20 mg/kg s.c.) was tested in 12-, 18-, and 25-day-old rats in three models of convulsive seizures. Pentylenetetrazol-induced generalized seizures with a loss of righting reflexes generated in the brainstem were suppressed in all three age groups in a dose-dependent manner. Minimal clonic seizures with preserved righting ability exhibited only moderately prolonged latency after the highest dose of PEAQX. Anticonvulsant action of all three doses of PEAQX against cortical epileptic afterdischarges (generated in the forebrain) was found in the 25-day-old animals. The highest dose (20 mg/kg) was efficient also in the two younger groups, which might be due to lower specificity of PEAQX and its partial affinity to the GluN2B subunit. Our results are in agreement with the postero-anterior maturation gradient of subunit composition of NMDA receptors (i.e., an increase of GluN2A representation). In spite of the lower selectivity of PEAQX, our data demonstrate, for the first time, developmental differences in comparison with an antagonist of NMDA receptors with a dominant GluN2B subunit.

• Keywords
• GluN2A subunit, NMDA receptors, anticonvulsant action, cortical epileptic afterdischarges, immature rats, pentylenetetrazol-induced seizures,
• Publication type
• Journal Article MeSH

Endo- as well as exogenous adenosine exhibits anticonvulsant action. Participation of individual types of adenosine receptors was studied in present experiments in immature rats. Cortical epileptic afterdischarges were used as a model in rat pups 12, 18 and 25 days old. CCPA, an agonist of A1 adenosine receptors, decreased markedly duration of afterdischarges whereas DPCPX, an antagonist of A1 receptors, exhibited strong proconvulsant action. Action of either drug was best expressed in 12-day-old rats and it decreased with age. Drugs influencing A2A adenosine receptors (agonist CGS21680 and antagonist ZM241385) did not exhibit systematic effects in our model. Motor phenomena accompanying cortical stimulation or epileptic afterdischarge were never influenced by any of the four drugs studied. A1 adenosine receptors are important in the model of cortical seizures, especially in the youngest group studied.

• MeSH
• Action Potentials drug effects   physiology   MeSH
• Analysis of Variance MeSH
• Biophysics MeSH
• Electric Stimulation MeSH
• Rats MeSH
• Cerebral Cortex cytology   growth & development   MeSH
• Animals, Newborn MeSH
• Rats, Wistar MeSH
• Purinergic Agents pharmacology   MeSH
• Receptor, Adenosine A1 metabolism   MeSH
• Receptors, Adenosine A2 metabolism   MeSH
• Age Factors MeSH
• Dose-Response Relationship, Drug MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Names of Substances
• Purinergic Agents MeSH
• Receptor, Adenosine A1 MeSH
• Receptors, Adenosine A2 MeSH

The time course of the anticonvulsant effect of vigabatrin against cortically induced epileptic after-discharges (ADs) was studied in freely moving rats with implanted electrodes. Adult rats (n=30) were exposed to five stimulation sessions each consisting of six stimulation series at 20-min intervals. The first session was a control one, then two groups of animals (n=10 each) were given vigabatrin (600 or 1,200 mg/kg i.p.), the control animals received physiological saline. Stimulation sessions were repeated 1, 24, 48, and 96 hours after the injection. Control animals exhibited an increased transition from the spike-and-wave type of AD to the second, "limbic" type and an increased intensity of movements accompanying stimulation. ADs in the second and subsequent sessions were, however, shorter than in the first session. Vigabatrin facilitated the transition to the second type of AD 1 h after administration but suppressed this transition as well as decreased the number of stimulations eliciting ADs 48 h later. AD duration and the severity of clonic seizures accompanying spike-and-wave ADs were influenced similarly. The effects of the lower dose of vigabatrin were more marked than those of the higher dose. The biphasic action of vigabatrin in our model might be due either to uneven changes of GABA concentration in different brain structures or to an additional mechanism of action. Our results in a cortical model of seizure demonstrate that the sequence of pro- and anticonvulsant actions of vigabatrin is not restricted to seizures of limbic origin and might represent a general phenomenon.

• MeSH
• Electroshock methods   MeSH
• Electroencephalography methods   MeSH
• Epilepsy chemically induced   physiopathology   prevention & control   MeSH
• Rats MeSH
• Cerebral Cortex drug effects   physiology   MeSH
• Rats, Wistar MeSH
• Vigabatrin therapeutic use   toxicity   MeSH
• Animals MeSH
• Check Tag
• Rats MeSH
• Male MeSH
• Animals MeSH
• Publication type
• Journal Article MeSH
• Research Support, Non-U.S. Gov't MeSH
• Comparative Study MeSH
• Names of Substances
• Vigabatrin MeSH