tolcapone and Brain-Ischemia

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.

Topics: Animals; Benzophenones; Brain Ischemia; Catechol O-Methyltransferase Inhibitors; Cell Survival; Cells, Cultured; Embryo, Mammalian; Enzyme Inhibitors; L-Lactate Dehydrogenase; Models, Neurological; Monoamine Oxidase Inhibitors; Neurons; Neuroprotective Agents; Nitrophenols; Prosencephalon; Rats; Rats, Sprague-Dawley; Selegiline; Time Factors; Tolcapone

Foetal rat brain aggregation cultures were exposed to a single episode of anoxia and hypoglycaemia for 30 min. Lactate dehydrogenase specific activity was estimated in the culture medium after ischaemia as a marker of lost cell integrity. Release of lactate dehydrogenase was most prominent during the first 24 hr period after the ischaemic damage, then it gradually declined. Immediately after ischaemic exposure, the cultures were treated with different concentrations of L-deprenyl or tolcapone. Significantly lower amounts of lactate dehydrogenase leaked into the culture medium during the first 24 hr after the ischaemic episode in cultures treated with deprenyl or tolcapone (1-100 nM). These results suggest that deprenyl and tolcapone may reduce cell damage after ischaemia, at doses causing enzyme inhibition.

Topics: Animals; Benzophenones; Brain Ischemia; Catechol O-Methyltransferase; Catechol O-Methyltransferase Inhibitors; Cell Hypoxia; Cells, Cultured; Cytoprotection; Drug Combinations; Female; Hypoglycemia; In Situ Nick-End Labeling; L-Lactate Dehydrogenase; Monoamine Oxidase; Monoamine Oxidase Inhibitors; Neuroprotective Agents; Nitrophenols; Pregnancy; Prosencephalon; Rats; Rats, Sprague-Dawley; Selegiline; Tolcapone