Role of lithium chloride and paraldehyde in acute changes after lithium-pilocarpine status epilepticus (SE) induced at postnatal day 12 was studied in 15-day-old rats. In addition to SE group four other groups were formed: naïve animals without any injection, lithium chloride group, paraldehyde group and lithium-paraldehyde group. Cortical epileptic afterdischarges (CxADs) induced by increasing intensities of stimulation current were used as a measure of excitability. SE animals did not exhibit any change in duration of CxADs with increasing stimulation intensity in contrast to naïve control with a progressive prolongation of CxAD. LiCl group was similar to SE rats whereas paraldehyde and lithium-paraldehyde groups exhibited some progress in duration of ADs. Lithium chloride participates in short-term changes of CxADs after SE. Paraldehyde and combination of lithium and paraldehyde are similar to naïve controls.
- MeSH
- antikonvulziva farmakologie MeSH
- chlorid lithný farmakologie MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra účinky léků MeSH
- paraldehyd farmakologie MeSH
- pilokarpin farmakologie MeSH
- potkani Wistar MeSH
- status epilepticus chemicky indukované MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Perinatal stroke is a common cerebrovascular disorder affecting 1 in every 4000 births; typically associated with epilepsy. We sought to determine seizure susceptibility to pentylentetrazol (PTZ)-induced seizures in developing rats with a history of photothrombotic lesion of sensorimotor cortex induced at postnatal day 7. Lesioned animals were tested at P12 or P25 and compared with sham-operated controls. Three models of epileptic seizures were elicited by PTZ: episodes of spike-and-wave rhythm, minimal clonic seizures and generalized tonic-clonic seizures. PTZ (60 and 100 mg/kg) was administered subcutaneously to assess seizure occurrence, latency and severity. In addition, episodes of rhythmic EEG activity were analyzed at P25 following successive interperitoneal 20 and 40 mg/kg PTZ administration. There was only one significant change in convulsive seizures--decreased latency of generalized seizures in lesioned 12-day-old animals. EEG study demonstrated marked difference between lesioned and control rats. Lesioned rats had longer latencies and longer durations of the first rhythmic episode (following 20 mg/kg PTZ) as compared to controls. After 40 mg/kg of PTZ, 7 in 8 leisioned and 1 in 8 control rats exhibited clonic seizures. Cortical ischemic lesion during early development affected differently the susceptibility of rat's brain to three types of PTZ-induced seizures 5 and 18 days post photothrombotic insults.
- MeSH
- cévní mozková příhoda komplikace MeSH
- elektroencefalografie MeSH
- epilepsie komplikace patofyziologie MeSH
- ischemie mozku komplikace MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- lasery MeSH
- modely nemocí na zvířatech MeSH
- mozek patologie patofyziologie MeSH
- pentylentetrazol farmakologie MeSH
- potkani Wistar MeSH
- záchvaty chemicky indukované komplikace patofyziologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
The activation of metabotropic glutamate receptors subtype 4 (mGluR4) potentiates models of absence seizures in adult rats. These seizures are age-dependent, but data concerning the role of mGluR4 in immature brain is insufficient. N-phenyl-7-(hydroxyimino)cyclopropa[b]chromen-1acarboxamide (PHCCC), which is a positive allosteric modulator of these receptors, was used in three different models of seizures in immature rats: 1) convulsions induced by high doses of pentetrazol (PTZ; a model of generalised tonic-clonic seizures); 2) rhythmic electro-encephalographic (EEG) activity induced by low doses of PTZ (a model of absence seizures); and 3) electrically elicited cortical afterdischarges (ADs, a model of myoclonic seizures). We administered four doses of PHCCC (1, 3, 10 and 20 mg/kg) in PTZ-induced convulsions and two doses (3 and 10 mg/kg) in the two electrophysiological models of freely moving rats with implanted electrodes. Every dose and age group consisted from 8 to 10 rats. PTZ-elicited convulsions were not significantly influenced by PHCCC. In contrast, PHCCC potentiated the effect of a subconvulsant dose (60 mg/kg) of PTZ. The 10-mg/kg dose of PHCCC significantly prolonged the duration of PTZ-induced rhythmic activity episodes and shortened the intervals between individual episodes in 25-day-old rats (P25). In contrast, this potentiation was not seen in P18 rats. Cortical ADs were significantly prolonged with repeated stimulations by both doses of PHCCC in P12 and P18 animals. P25 rats exhibited only slightly longer AD durations. In conclusion, we did not find any anticonvulsant effect of PHCCC. On the contrary, proconvulsant action was demonstrated in all three models in immature rats.
- MeSH
- benzopyrany aplikace a dávkování farmakologie MeSH
- elektroencefalografie MeSH
- epilepsie farmakoterapie etiologie metabolismus MeSH
- konvulzíva aplikace a dávkování farmakologie MeSH
- krysa rodu rattus MeSH
- modely nemocí na zvířatech MeSH
- mozková kůra účinky léků patofyziologie MeSH
- novorozená zvířata MeSH
- potkani Wistar MeSH
- receptory metabotropního glutamátu metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Repeated caffeine treatment during early postnatal period led to a decreased sensitivity to convulsant action of drugs interfering with inhibitory systems. To know if it is a general effect we studied convulsant action of agonists of glutamate receptors N-methyl-d-aspartate (NMDA) and kainic acid (KA). Early (the first day after the last injection) and delayed (at postnatal day (P) 25) consequences of daily administration of caffeine at P7-P11 or P13-P17 days were studied. Two doses (one submaximal and one supramaximal) of either drug were chosen for each age group on the basis of our older data demonstrating decreasing sensitivity during postnatal development. Both early and delayed proconvulsant effects of submaximal doses of either agonist were observed in P7-P11 groups, early effect was markedly expressed; the effects of the supramaximal doses were not affected. The other administration group (P13-P17) also exhibited an increased sensitivity to convulsant action but delayed effects were more pronounced than early consequences especially with supramaximal doses of both agonists. In contrast to a decreased sensitivity to drugs suppressing inhibitory systems, seizures induced by glutamate receptor agonists are potentiated in caffeine-treated immature rats. Timing of caffeine administration and interval between the last exposure and testing play an important role.
- MeSH
- agonisté excitačních aminokyselin farmakologie MeSH
- analýza rozptylu MeSH
- časové faktory MeSH
- kofein aplikace a dávkování škodlivé účinky MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- kyselina kainová farmakologie MeSH
- N-methylaspartát farmakologie MeSH
- náchylnost k nemoci * etiologie metabolismus MeSH
- potkani Wistar MeSH
- receptory kyseliny kainové metabolismus MeSH
- receptory N-methyl-D-aspartátu metabolismus MeSH
- věkové faktory MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- záchvaty * etiologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
PURPOSE: Antagonists of group I metabotropic glutamate receptors (mGluRs) are known to exhibit anticonvulsant action without serious side effects. Recently we found anticonvulsant effects of specific antagonists of mGluR subtypes 1 and 5 (AIDA and MTEP) against pentetrazol-induced convulsions in developing rats. In order to determine if the effects of these two antagonists are not exclusively restricted to pentetrazol-induced seizures, we studied their action in a novel seizure model involving immature rats. METHODS: Epileptic afterdischarges were elicited by low-frequency stimulation of sensorimotor cortical region in 12-, 18-, and 25-day-old rats with implanted electrodes. Drugs were administered intraperitoneally after the first afterdischarge: AIDA in doses from 5 to 40 mg/kg; MTEP in doses from 2.5 to 40 mg/kg. The stimulation was then repeated five more times with the same current intensity. Electrocorticographic and motor phenomena were recorded and evaluated. RESULTS: AIDA did not significantly influence movements during stimulation, afterdischarges as well as clonic seizures accompanying afterdischarges. In contrast, MTEP was able to significantly shorten afterdischarges without changes in the two motor phenomena. The effect of MTEP was best expressed in 12-day-old rats; in 25-day-old rats the trials exhibited only a transient shortening of afterdischarges after high doses of MTEP. DISCUSSION: In contrast to similar action against pentetrazol-induced seizures, AIDA and MTEP substantially differ in their action on cortical epileptic afterdischarges. The anticonvulsant action of MTEP in the present model diminishes with age.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- antikonvulziva farmakologie MeSH
- elektroencefalografie statistika a číselné údaje MeSH
- epilepsie chemicky indukované patofyziologie prevence a kontrola MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- mozková kůra patofyziologie účinky léků MeSH
- novorozená zvířata MeSH
- pentylentetrazol farmakologie MeSH
- pohybová aktivita fyziologie účinky léků MeSH
- potkani Wistar MeSH
- pyridiny farmakologie MeSH
- receptory metabotropního glutamátu antagonisté a inhibitory MeSH
- receptory N-methyl-D-aspartátu MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- financování organizované MeSH
The present study has examined the anticonvulsant and neuroprotective effect of 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC), a selective agonist for group II metabotropic glutamate receptors (mGluRs) when given 10-15 min after the onset of seizures induced in 12-day-old rats by bilateral icv infusion of DL-homocysteic acid (DL-HCA, 600 nmol/side). For biochemical analyses, rat pups were sacrificed during generalized clonic-tonic seizures, approximately 45-50 min after infusion of DL-HCA. Comparable time intervals were used for sacrificing the animals which received 2R,4R-APDC (0.05 nmol/side) or saline. The severity of seizures was influenced only slightly when the agonist was given after the onset of seizures, as evaluated both from the behavioral symptoms and from EEG recordings. A tendency to lower number and a shorter duration of seizures was outlined in animals posttreated with 2R,4R-APDC, but the differences did not reach the level of statistical significance. Cortical energy metabolite changes which normally accompany seizures in immature rats (large decrease of glucose and glycogen and a marked rise of lactate) were ameliorated only partially. The neuroprotective effect of 2R,4R-APDC was evaluated after 24 h and 6 days of survival following DL-HCA-induced seizures. Massive neuronal degeneration in many brain regions, mainly in the hippocampus and thalamus, following infusion of DL-HCA alone was only partially attenuated after 2R,4R-APDC posttreatment. The present findings clearly indicate that both anticonvulsant and neuroprotective effect of 2R,4R-APDC against DL-HCA-induced seizures is substantially diminished when the agonist is given after the onset of seizures as compared with its efficacy after the pretreatment (Exp. Neurol.192, 420-436, 2005).
- MeSH
- agonisté excitačních aminokyselin terapeutické užití MeSH
- cytoprotekce fyziologie účinky léků MeSH
- degenerace nervu chemicky indukované patofyziologie prevence a kontrola MeSH
- epilepsie farmakoterapie metabolismus patofyziologie MeSH
- hipokampus metabolismus růst a vývoj účinky léků MeSH
- homocystein analogy a deriváty farmakologie MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- lékové interakce fyziologie MeSH
- mozek metabolismus růst a vývoj účinky léků MeSH
- neuroprotektivní látky terapeutické užití MeSH
- potkani Wistar MeSH
- prolin analogy a deriváty terapeutické užití MeSH
- receptory metabotropního glutamátu agonisté metabolismus MeSH
- rozvrh dávkování léků MeSH
- stárnutí metabolismus MeSH
- thalamus metabolismus růst a vývoj účinky léků MeSH
- výsledek terapie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
Typical N-methyl-D-aspartate (NMDA) receptor antagonists exhibit anticonvulsant action and unwanted effects, even in developing rats. Therefore, we studied the actions of the low-affinity, noncompetitive antagonist memantine and the NR2B-specific antagonist ifenprodil. Seizures (minimal clonic and generalized tonic-clonic) were elicited with pentylenetetrazol (100mg/kg subcutaneously) in rats 7, 12, 18, and 25 days old pretreated with memantine (2.5-40 mg/kg intraperitoneally) or ifenprodil (10-60 mg/kg intraperitoneally). The effects of both drugs were studied in open field and motor performance tests in 12-, 18-, and 25-day-old rats. Memantine suppressed generalized tonic-clonic seizures in all age groups; minimal seizures were potentiated. Ifenprodil abolished the tonic phase of generalized tonic-clonic seizures in 7-, 12-, and 18-day-old rats only; minimal seizures remained untouched. Memantine induced locomotor hyperactivity and compromised motor performance in all age groups. Ifenprodil exerted these effects only in 12-day-old rats; older animals were less active in open field tests. Memantine exhibits both anti- and pro-convulsant and behavioral effects typical of NMDA antagonists. Ifenprodil exerted the same effects in 12-day-old rats, but its anticonvulsant action in 18-day-old rats was accompanied by a decrease in locomotion.
- MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- antikonvulziva farmakologie MeSH
- chování zvířat účinky léků MeSH
- epilepsie generalizovaná psychologie MeSH
- financování organizované MeSH
- konvulzíva antagonisté a inhibitory farmakologie MeSH
- krysa rodu rattus MeSH
- memantin farmakologie MeSH
- orientace účinky léků MeSH
- pentylentetrazol analogy a deriváty farmakologie MeSH
- piperidiny farmakologie MeSH
- pohybová aktivita účinky léků MeSH
- posturální rovnováha účinky léků MeSH
- potkani Wistar MeSH
- psychomotorický výkon účinky léků MeSH
- receptory N-methyl-D-aspartátu antagonisté a inhibitory MeSH
- síla ruky fyziologie MeSH
- učení účinky léků MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- záchvaty farmakoterapie psychologie MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- zvířata MeSH
Some age-dependent epilepsies of infancy and childhood cannot be sufficiently treated with contemporaneous antiepileptics, therefore search for new mechanisms and new drugs active in pediatric patients is necessary. Possible anticonvulsant action of AMN082 (N,N'-dibenzhydryl-ethane-1,2-diamine dihydrochloride), a positive allosteric modulator of metabotropic glutamate receptor subtype 7, was examined in a model of epileptic afterdischarges elicited in three age groups of immature rats (12, 18 and 25days old) by electrical stimulation of sensorimotor cortex. AMN082 did not exhibit an anticonvulsant action against spike-and-wave type of afterdischarges generated in the thalamocortical system; on the contrary, moderate proconvulsant action was found in 12- and 18-day-old rats (more marked prolongation of afterdischarges with repeated stimulations). On the other hand, AMN082 significantly shortened the second type of afterdischarges reflecting spread of epileptic activity into limbic system frequently recorded in 25-day-old rats. These contradictory results mean that AMN082 will not be a broad-spectrum anticonvulsant but it might be useful as a seizure-specific antiepileptic drug.
- MeSH
- antikonvulziva farmakologie MeSH
- benzhydrylové sloučeniny kontraindikace terapeutické užití MeSH
- epilepsie farmakoterapie MeSH
- hluboká mozková stimulace metody MeSH
- implantované elektrody MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus MeSH
- látky působící na systém excitačních aminokyselin kontraindikace terapeutické užití MeSH
- limbický systém účinky léků MeSH
- potkani Wistar MeSH
- receptory metabotropního glutamátu metabolismus MeSH
- stárnutí MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- práce podpořená grantem MeSH
- MeSH
- antikonvulziva farmakologie MeSH
- epilepsie tonicko-klonická farmakoterapie chemicky indukované MeSH
- finanční podpora výzkumu jako téma MeSH
- glutamátové receptory účinky léků MeSH
- konvulzíva farmakologie MeSH
- krysa rodu rattus růst a vývoj MeSH
- kyselina kainová farmakologie MeSH
- receptory N-methyl-D-aspartátu agonisté antagonisté a inhibitory účinky léků MeSH
- zvířata MeSH
- Check Tag
- krysa rodu rattus růst a vývoj MeSH
- zvířata MeSH
