Nejvíce citovaný článek - PubMed ID 2975798
Epileptic phenomena produced by kainic acid in laboratory rats during ontogenesis
Seizures elicited by corneal 6-Hz stimulation are widely acknowledged as a model of temporal lobe seizures. Despite the intensive research in rodents, no studies hint at this model in developing animals. We focused on seven age groups of both male and female rats. Biphasic pulses with 0.3 ms duration and current intensities from 20 to 80 mA were applied transcorneally for 3 s to calculate threshold intensities for individual age groups. Threshold stimulation intensity necessary for elicitation of clonic seizures was highly age- and sex-dependent. The highest threshold was observed in the youngest (15-day-old) group then it decreased to the age of 25 days and increased again up to adulthood. The threshold current tended to be lower in females of all age groups. The incidence of convulsive seizures increased with stimulation intensity up to postnatal day 25 in either sex. In rats of 31 days old and older convulsions occurred irregularly regardless of the stimulation current and sex. For subsequent analysis, the animals were categorized into two groups: juveniles, aged 15 to 25 days, and adolescents/adults, aged 31 days and older. Our statistical analyses revealed an increased risk of convulsions after the stimulation with higher intensities in juvenile but not adolescent/adult rats. Females tended to be more sensitive to the stimulation with lower currents than males. Seizure severity was higher in females 18- to 25-day old compared to males of the same age and the seizure duration increased with stimulation intensities in juvenile but not adolescent/adult animals. The data extend the use of the rat 6 Hz model to immature animals and may be useful as a model of pediatric temporal lobe seizures.
- MeSH
- elektrická stimulace * MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- rohovka patofyziologie patologie MeSH
- věkové faktory MeSH
- záchvaty * patofyziologie etiologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
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
- akademie a ústavy MeSH
- biomedicínský výzkum trendy MeSH
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- epilepsie * patofyziologie MeSH
- lidé MeSH
- mozek účinky léků fyziologie růst a vývoj MeSH
- zvířata MeSH
- Check Tag
- dějiny 20. století MeSH
- dějiny 21. století MeSH
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy MeSH
- Geografické názvy
- Česká republika MeSH
LiCl/pilocarpine status epilepticus (SE) induced in immature rats leads, after a latent period, to hippocampal hyperexcitability. The excitability may be influenced by adenosine, which exhibits anticonvulsant activity. The concentration of adenosine is regulated by adenosine kinase (ADK) present in two isoforms-ADK-L and ADK-S. The main goal of the study is to elucidate the changes in ADK isoform expression after LiCl/pilocarpine SE and whether potential changes, as well as inhibition of ADK by 5-iodotubercidin (5-ITU), may contribute to changes in hippocampal excitability during brain development. LiCl/pilocarpine SE was elicited in 12-day-old rats. Hippocampal excitability in immature rats was studied by the model of hippocampal afterdischarges (ADs), in which we demonstrated the potential inhibitory effect of 5-ITU. ADs demonstrated significantly decreased hippocampal excitability 3 days after SE induction, whereas significant hyperexcitability after 20 days compared to controls was shown. 5-ITU administration showed its inhibitory effect on the ADs in 32-day-old SE rats compared to SE rats without 5-ITU. Moreover, both ADK isoforms were examined in the immature rat hippocampus. The ADK-L isoform demonstrated significantly decreased expression in 12-day-old SE rats compared to the appropriate naïve rats, whereas increased ADK-S isoform expression was revealed. A decreasing ADK-L/-S ratio showed the declining dominance of ADK-L isoform during early brain development. LiCl/pilocarpine SE increased the excitability of the hippocampus 20 days after SE induction. The ADK inhibitor 5-ITU exhibited anticonvulsant activity at the same age. Age-related differences in hippocampal excitability after SE might correspond to the development of ADK isoform levels in the hippocampus.
- Klíčová slova
- LiCl/pilocarpine, adenosine kinase, development, epileptic afterdischarges, hippocampus, inhibitor, isoforms, rat, status epilepticus,
- MeSH
- adenosin metabolismus MeSH
- adenosinkinasa metabolismus MeSH
- antikonvulziva farmakologie MeSH
- hipokampus metabolismus MeSH
- krysa rodu Rattus MeSH
- modely nemocí na zvířatech MeSH
- pilokarpin * toxicita MeSH
- protein - isoformy metabolismus MeSH
- status epilepticus * chemicky indukované farmakoterapie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- adenosin MeSH
- adenosinkinasa MeSH
- antikonvulziva MeSH
- pilokarpin * MeSH
- protein - isoformy MeSH
Objective: The adenosinergic system may influence excitability in the brain. Endogenous and exogenous adenosine has anticonvulsant activity presumably by activating A1 receptors. Adenosine A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA) may thus bolster anticonvulsant effects, but its action and the number of A1 receptors at different developmental stages are not known. Methods: Hippocampal epileptic afterdischarges (ADs) were elicited in 12-, 15-, 18-, 25-, 45-, and 60-day-old rats. Stimulation and recording electrodes were implanted into the dorsal hippocampus. The A1 receptor agonist 2-chloro-N6-cyclopentyladenosine (CCPA, 0.5 or 1 mg/kg) was administered intraperitoneally 10 min before the first stimulation. Control animals were injected with saline. All rats were stimulated with a 2-s series of 1-ms biphasic pulses delivered at 60 Hz with increasing stepwise intensity (0.05-0.6 mA). Each age and dose group contained 9-14 animals. The AD thresholds and durations were evaluated, and the A1 receptors were detected in the hippocampus in 7-, 10-, 12-, 15-, 18-, 21-, 25-, 32-, and 52-day-old rats. Results: Both CCPA doses significantly increased hippocampal AD thresholds in 12-, 15-, 18-, and 60-day-old rats compared to controls. In contrast, the higher dose significantly decreased AD threshold in the 25-day-old rats. The AD durations were significantly shortened in all age groups except for 25-day-old rats where they were significantly prolonged. A1 receptor expression in the hippocampus was highest in 10-day-old rats and subsequently decreased. Significance: The adenosine A1 receptor agonist CCPA exhibited anticonvulsant activity at all developmental stages studied here except for 25-day-old rats. Age-related differences might be due to the development of presynaptic A1 receptors in the hippocampus.
- Klíčová slova
- adenosine receptor, agonist, development, epileptic afterdischarges, hippocampus, rat,
- Publikační typ
- časopisecké články MeSH
A quantitative description of motor seizures induced by pentylenetetrazol (PTZ, metrazol) was performed. Seizures were induced by PTZ in doses from 40 to 120 mg/kg s.c. in 477 male albino rats of the Wistar strain 7 to 90 days old. Two patterns of seizures were elicited: minimal, i.e. predominantly clonic seizures of facial and forelimb muscles with preserved righting ability, and major, i.e. generalized tonic-clonic seizures with a loss of righting reflex. Minimal seizures could be reliably elicited since the age of 18 days; the CD50 for these seizures did not significantly differ with age. Major seizures were elicited regularly at all developmental stages studied. Their CD50 did not significantly differ among 7-, 12- and 25-day-old rat pups but the value for 18-day-old rats was smaller and for adult animals larger than these three age groups.
- MeSH
- epilepsie tonicko-klonická chemicky indukované patofyziologie MeSH
- injekce subkutánní MeSH
- krysa rodu Rattus MeSH
- pentylentetrazol * MeSH
- potkani Wistar MeSH
- stárnutí fyziologie MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- záchvaty chemicky indukované patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Názvy látek
- pentylentetrazol * MeSH