Document Detail

Posttreatment with group II metabotropic glutamate receptor agonist 2R,4R-4-aminopyrrolidine-2,4-dicarboxylate is only weakly effective on seizures in immature rats.
MedLine Citation:
PMID:  19341715     Owner:  NLM     Status:  MEDLINE    
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).
Jaroslava Folbergrová; Rastislav Druga; Grygoriy Tsenov; Renata Haugvicová; Jakub Otáhal
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2009-03-31
Journal Detail:
Title:  Brain research     Volume:  1273     ISSN:  1872-6240     ISO Abbreviation:  Brain Res.     Publication Date:  2009 Jun 
Date Detail:
Created Date:  2009-05-26     Completed Date:  2009-08-14     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0045503     Medline TA:  Brain Res     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  144-54     Citation Subset:  IM    
Institute of Physiology, v.v.i., Academy of Sciences of the Czech Republic, Vídenská 1083, 142 20 Prague 4, Czech Republic.
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MeSH Terms
Aging / metabolism
Brain / drug effects*,  growth & development,  metabolism
Convulsants / pharmacology
Cytoprotection / drug effects,  physiology
Drug Administration Schedule
Drug Interactions / physiology
Epilepsy / drug therapy*,  metabolism,  physiopathology
Excitatory Amino Acid Agonists / therapeutic use*
Hippocampus / drug effects,  growth & development,  metabolism
Homocysteine / analogs & derivatives,  pharmacology
Nerve Degeneration / chemically induced,  physiopathology,  prevention & control
Neuroprotective Agents / therapeutic use*
Proline / analogs & derivatives*,  therapeutic use
Rats, Wistar
Receptors, Metabotropic Glutamate / agonists*,  metabolism
Thalamus / drug effects,  growth & development,  metabolism
Treatment Outcome
Reg. No./Substance:
0/4-aminopyrrolidine-2,4-dicarboxylic acid; 0/Convulsants; 0/Excitatory Amino Acid Agonists; 0/Neuroprotective Agents; 0/Receptors, Metabotropic Glutamate; 0/metabotropic glutamate receptor 2; 1001-13-4/homocysteic acid; 147-85-3/Proline; 454-28-4/Homocysteine

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