A cell culture model of cerebral ischemia as a convenient system to screen for neuroprotective drugs.
Aggregation cultures of rat brain were exposed to a combination of anoxia and hypoglycaemia for 30 minutes. Thereafter, the release of lactate dehydrogenase into the cell culture medium was monitored up to 4 days as a measure of cell damage after the ischemic insult. Some cultures were treated with different concentrations of deprenyl or tolcapone, selective inhibitors of monoamine oxidase B and catechol-O-methyltransferase, respectively. After 1 day in culture, the release of lactate dehydrogenase was significantly reduced in cultures treated with deprenyl (at 1 nM. 100 nM, and 10 microM), as well as in cultures treated with 1 nM or 100 nM tolcapone; 10 microM of tolcapone, on the other hand, resulted in a toxic effect on the cell aggregates. No differences in the release of lactate dehydrogenase into the medium was observed in the aggregates treated with drugs as compared with the control cultures after 2 or 4 days post-ischemia.
Ekblom
J
J
Department of Medical Pharmacology, Uppsala University, Sweden.
Garpenstrand
H
H
Tottmar
O
O
Prince
J A
JA
Oreland
L
L
D000818:Animals; D001577:Benzophenones / Q000494:pharmacology*; D002545:Brain Ischemia; D065098:Catechol O-Methyltransferase Inhibitors; D002470:Cell Survival / Q000187:drug effects*; D002478:Cells, Cultured; D004622:Embryo, Mammalian; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D007770:L-Lactate Dehydrogenase; D008959:Models, Neurological; D008996:Monoamine Oxidase Inhibitors / Q000494:pharmacology*; D009474:Neurons / Q000166:cytology* / Q000187:drug effects; D018696:Neuroprotective Agents / Q000494:pharmacology*; D009596:Nitrophenols; D016548:Prosencephalon / Q000166:cytology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012642:Selegiline / Q000494:pharmacology*; D013997:Time Factors; D000077867:Tolcapone
D001577:Benzophenones; D065098:Catechol O-Methyltransferase Inhibitors; D004791:Enzyme Inhibitors; D008996:Monoamine Oxidase Inhibitors; D018696:Neuroprotective Agents; D009596:Nitrophenols; D012642:Selegiline; D000077867:Tolcapone; D007770:L-Lactate Dehydrogenase