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
Language English Country United States Media print
Document type Comparative Study, Journal Article, Research Support, Non-U.S. Gov't
PubMed
15755559
DOI
10.1016/j.expneurol.2004.12.019
PII: S0014-4886(04)00542-4
Knihovny.cz E-resources
- MeSH
- Amino Acids pharmacology MeSH
- Excitatory Amino Acid Antagonists pharmacology MeSH
- Anticonvulsants therapeutic use MeSH
- Time Factors MeSH
- Behavior, Animal MeSH
- Nerve Degeneration pathology prevention & control MeSH
- Electroencephalography methods MeSH
- Fluoresceins MeSH
- Fluorescent Dyes MeSH
- Functional Laterality MeSH
- Glucose metabolism MeSH
- Glycogen metabolism MeSH
- Homocysteine analogs & derivatives MeSH
- Rats MeSH
- Lactic Acid metabolism MeSH
- Drug Interactions MeSH
- Brain Chemistry drug effects MeSH
- Brain anatomy & histology drug effects physiopathology MeSH
- Animals, Newborn MeSH
- Organic Chemicals MeSH
- Brain Injuries etiology prevention & control MeSH
- Rats, Wistar MeSH
- Proline analogs & derivatives therapeutic use MeSH
- Receptors, Metabotropic Glutamate agonists MeSH
- Dose-Response Relationship, Drug MeSH
- Xanthenes pharmacology MeSH
- Seizures chemically induced complications 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
- 4-aminopyrrolidine-2,4-dicarboxylic acid MeSH Browser
- Amino Acids MeSH
- Excitatory Amino Acid Antagonists MeSH
- Anticonvulsants MeSH
- Fluoresceins MeSH
- Fluorescent Dyes MeSH
- fluoro jade MeSH Browser
- Glucose MeSH
- Glycogen MeSH
- homocysteic acid MeSH Browser
- Homocysteine MeSH
- Lactic Acid MeSH
- LY 341495 MeSH Browser
- Organic Chemicals MeSH
- Proline MeSH
- Receptors, Metabotropic Glutamate MeSH
- Xanthenes 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.
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