Action of antiepileptic drugs in immature brain may differ from that in adult brain. The aim of our study was to study an anticonvulsant action of lamotrigine and phenytoin, i.e. two drugs active against partial seizures in adult experimental animals as well as human patients, in a model of simple partial seizures in immature rats. Epileptic foci were induced by local application of bicuculline methiodide on sensorimotor cortical area of 12-day-old rat pups. The animals were pretreated with lamotrigine (LTG, 10 or 20 mg/kg i.p.) or phenytoin (PHT, 15, 30 or 60 mg/kg i.p.). Control rats for LTG received saline, controls for PHT solvent composed of propyleneglycol, ethanol and water. Influence of either drug on interictal activity was negligible. High doses of both LTG and PHT suppressed the transition into ictal phases and shortened the duration of persisting seizures. The tricomponent solvent exhibited moderate activity against ictal activity if compared with saline controls. The two drugs exhibited similar action in our model, i.e. the suppression of secondary generalization from epileptic focus. This action is comparable to that described for human patients and adult experimental animals. In favor of lamotrigine speaks the absence of serious side effects.
- MeSH
- bikukulin analogy a deriváty MeSH
- časové faktory MeSH
- elektroencefalografie MeSH
- epilepsie parciální chemicky indukované patofyziologie prevence a kontrola MeSH
- fenytoin farmakologie MeSH
- financování organizované MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- motorické korové centrum patofyziologie účinky léků MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- triaziny farmakologie MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- srovnávací studie MeSH
GABA exhibits depolarizing action in the immature neurons due to high intracellular activity of chloride ions. It is maintained by cation-chloride cotransporter NKCC1 which is present in immature brain. Bumetanide is a specific inhibitor of this cotransporter. We studied possible anticonvulsant activity of bumetanide in pentylenetetrazol-induced seizures in three age groups of rat pups (7, 12, and 18 days old). Pretreatment with bumetanide (0.2-1 mg/kg i.p.) resulted in dose-dependent decrease of incidence of the tonic phase of generalized tonicclonic seizures in 12-day-old rats only. No effect was observed in younger and older animals. Higher dose of bumetanide (2.5 mg/kg) did not affect tonic convulsions but, on the contrary, decreased latencies of generalized seizures in 12-day-old animals. Lack of marked anticonvulsant effect is probably due to relative maturity of neurons in the brainstem where the generator of generalized seizures is localized. Age- and dosespecific suppression of the tonic phase needs further analysis.
- MeSH
- antikonvulziva farmakologie MeSH
- bumetanid farmakologie MeSH
- epilepsie tonicko-klonická chemicky indukované metabolismus prevence a kontrola MeSH
- financování organizované MeSH
- GABA metabolismus MeSH
- inhibitory Na-K-Cl symportérů farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- pentylentetrazol MeSH
- potkani Wistar MeSH
- reakční čas MeSH
- sodík-draslík-chloridové symportéry metabolismus účinky léků MeSH
- stárnutí MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
Lithium-pilocarpine status epilepticus (SE) resulted in delayed changes of single cortical interhemisperic (transcallosal) responses in immature rats. Low-frequency stimulation inducing depression and/or potentiation was studied to analyze possible dynamic changes in cortical responses. Status was elicited in 12-day-old (SE12) or 25-day-old (SE25) rats. Control siblings received saline instead of pilocarpine. Interhemispheric responses were elicited by stimulation of the sensorimotor region of the cerebral cortex 3, 6, 9, 13, or 26 days after status. A series of 5 biphasic pulses with intensity equal to twofold threshold were used for stimulation. The interval between pulses was 100, 125, 160, 200 or 300 ms, eight responses were always averaged. Peak amplitude of the first positive, first negative and second positive waves was measured and responses to the second, third, fourth and fifth pulse were compared with the first one. Animals after status epilepticus as well as lithium-paraldehyde controls exhibit a frequency depression at nearly all the intervals studied. An outlined increase of responses in SE rats in comparison with the controls three days after SE stayed just below the level of statistical significance. In addition, animals in the SE12 group exhibited potentiation of responses at this interval after SE. With longer intervals after SE, the relation between SE and control animals changed twice resulting in a tendency to lower amplitude of responses in SE than in control rats 26 days after SE. Rats in the SE25 group exhibited higher responses than controls 13 days after status, but this difference was not present at the longest interval after SE. Low-frequency stimulation did not reveal increased cortical excitability as a long-lasting consequence of status epilepticus induced in immature rats. In addition, the outlined differences between SE and control rats changed with the time after SE.
- MeSH
- deprese etiologie patofyziologie MeSH
- epilepsie enzymologie etiologie patofyziologie MeSH
- evokované potenciály účinky léků MeSH
- financování organizované MeSH
- implantované elektrody virologie MeSH
- interpretace statistických dat MeSH
- pilokarpin škodlivé účinky MeSH
- potkani Wistar MeSH
- vývojová biologie metody MeSH
- MeSH
- chlorid lithný MeSH
- finanční podpora výzkumu jako téma MeSH
- krysa rodu rattus MeSH
- mozková kůra enzymologie patologie MeSH
- pilokarpin MeSH
- respirační komplex IV metabolismus MeSH
- status epilepticus enzymologie chemicky indukované patologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- abstrakt z konference MeSH
