title: Protective effect of group I metabotropic glutamate receptor activation against hypoxic/hypoglycemic injury in rat hippocampal slices: timing and involvement of protein kinase C.
abstract: Excessive release of glutamate during ischemia leads to sustained neuronal damage. In this study we investigated the influence of metabotropic glutamate receptor (mGluR) activation on neuronal recovery from a hypoxic/hypoglycemic event in hippocampal slices from rats. The slices were transiently exposed to an oxygen- and glucose-free environment in an interface chamber and the synaptically evoked population spike in the CA1 region was taken as a measure of neuronal viability. Under control conditions the population spike amplitude recovered to 41.4% of baseline value within 1 h after hypoxia/hypoglycemia. The specific mGluR group I agonist 3,5-dihydroxyphenylglycine (DHPG, 10 microM) increased the recovery rate to 88.3% of baseline value when applied from 20 min before until 10 min after the event. Similar recovery rates were obtained when DHPG was present only 10 or 20 min before hypoxia/hypoglycemia (89.3% and 79.3% of baseline value, respectively). However, when applied later, DHPG had no protective effect. Co-application of the protein kinase C (PKC) inhibitors staurosporine (100 nM) or chelerythrine (30 microM) prevented the protective effect of DHPG. Our data suggest that group I mGluR agonists are only protective when present prior to the onset of the hypoxic/hypoglycemic event and that the activation of PKC is a critical step of the protective mechanism.
authors.affiliation: Department of Neurophysiology, Federal Institute for Neurobiology, Magdeburg, Germany. schroede@ifn-magdeburg.de
authors.forename: U H
authors.initials: UH
authors.lastname: Schröder
authors.forename: T
authors.initials: T
authors.lastname: Opitz
authors.forename: T
authors.initials: T
authors.lastname: Jäger
authors.forename: C F
authors.initials: CF
authors.lastname: Sabelhaus
authors.forename: J
authors.initials: J
authors.lastname: Breder
authors.forename: K G
authors.initials: KG
authors.lastname: Reymann
mesh_terms: D000470:Alkaloids; D000818:Animals; D053119:Benzophenanthridines; D015687:Cell Hypoxia; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005071:Evoked Potentials / Q000187:drug effects*; D006624:Hippocampus / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D007003:Hypoglycemia; D066298:In Vitro Techniques; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000494:pharmacology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D010617:Phenanthridines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018094:Receptors, Metabotropic Glutamate / Q000819:agonists / Q000502:physiology*; D019311:Staurosporine / Q000494:pharmacology; D013997:Time Factors
chemical_list: D000470:Alkaloids; D053119:Benzophenanthridines; D004791:Enzyme Inhibitors; D018696:Neuroprotective Agents; D010617:Phenanthridines; D018094:Receptors, Metabotropic Glutamate; D008734:Methoxyhydroxyphenylglycol; C016299:chelerythrine; D011493:Protein Kinase C; D019311:Staurosporine; C010117:3,4-dihydroxyphenylglycol