Seizures induced in immature rats by homocysteic acid and the associated brain damage are prevented by group II metabotropic glutamate receptor agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate
Jazyk angličtina Země Spojené státy americké Médium print
Typ dokumentu srovnávací studie, časopisecké články, práce podpořená grantem
PubMed
15755559
DOI
10.1016/j.expneurol.2004.12.019
PII: S0014-4886(04)00542-4
Knihovny.cz E-zdroje
- MeSH
- aminokyseliny farmakologie MeSH
- antagonisté excitačních aminokyselin farmakologie MeSH
- antikonvulziva terapeutické užití MeSH
- časové faktory MeSH
- chování zvířat MeSH
- degenerace nervu patologie prevence a kontrola MeSH
- elektroencefalografie metody MeSH
- fluoresceiny MeSH
- fluorescenční barviva MeSH
- funkční lateralita MeSH
- glukosa metabolismus MeSH
- glykogen metabolismus MeSH
- homocystein analogy a deriváty MeSH
- krysa rodu Rattus MeSH
- kyselina mléčná metabolismus MeSH
- lékové interakce MeSH
- mozek - chemie účinky léků MeSH
- mozek anatomie a histologie účinky léků patofyziologie MeSH
- novorozená zvířata MeSH
- organické látky MeSH
- poranění mozku etiologie prevence a kontrola MeSH
- potkani Wistar MeSH
- prolin analogy a deriváty terapeutické užití MeSH
- receptory metabotropního glutamátu agonisté MeSH
- vztah mezi dávkou a účinkem léčiva MeSH
- xantheny farmakologie MeSH
- záchvaty chemicky indukované komplikace MeSH
- zvířata MeSH
- Check Tag
- krysa rodu Rattus MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- srovnávací studie MeSH
- Názvy látek
- 4-aminopyrrolidine-2,4-dicarboxylic acid MeSH Prohlížeč
- aminokyseliny MeSH
- antagonisté excitačních aminokyselin MeSH
- antikonvulziva MeSH
- fluoresceiny MeSH
- fluorescenční barviva MeSH
- fluoro jade MeSH Prohlížeč
- glukosa MeSH
- glykogen MeSH
- homocysteic acid MeSH Prohlížeč
- homocystein MeSH
- kyselina mléčná MeSH
- LY 341495 MeSH Prohlížeč
- organické látky MeSH
- prolin MeSH
- receptory metabotropního glutamátu MeSH
- xantheny MeSH
The present study has examined the anticonvulsant and neuroprotective effect of group II metabotropic glutamate receptor (mGluR) agonist (2R,4R)-4-aminopyrrolidine-2,4-dicarboxylate (2R,4R-APDC) in the model of seizures induced in immature 12-day-old rats by bilateral intracerebroventricular 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. Comparable time intervals were used for sacrificing the pups which had received 2R,4R-APDC. Low doses of 2R,4R-APDC (0.05 nmol/side) provided a pronounced anticonvulsant effect which was abolished by pretreatment with a selective group II mGluR antagonist LY341495. Generalized clonic-tonic seizures were completely suppressed and cortical energy metabolite changes which normally accompany these seizures were either normalized (decrease of glucose and glycogen) or markedly reduced (an accumulation of lactate). EEG recordings support the marked anticonvulsant effect of 2R,4R-APDC, nevertheless, this was only partial. In spite of the absence of obvious motor phenomena, isolated spikes or even short periods of partial ictal activity could be observed. Isolated spikes could also be seen in some animals after application of 2R,4R-APDC alone, reflecting most likely subclinical proconvulsant activity of this agonist. 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, as revealed by Fluoro-Jade B staining, was observed in a number of brain regions following infusion of DL-HCA alone (seizure group), whereas 2R,4R-APDC pretreatment provided substantial neuroprotection. The present findings support the possibility that group II mGluRs are a promising target for a novel approach to treating epilepsy.
Citace poskytuje Crossref.org
