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 ano xia and hypoglycaemia for 30 minutes. Thereafter, the release of lacta te dehydrogenase into the cell culture medium was monitored up to 4 da ys as a measure of cell damage after the ischemic insult. Some culture s were treated with different concentrations of deprenyl or tolcapone, selective inhibitors of monoamine oxidase B and catechol-O-methyltran sferase, respectively. After 1 day in culture, the release of lactate dehydrogenase was significantly reduced in cultures treated with depre nyl (at 1 nM, 100 nM, and 10 mu M), as well as in cultures treated wit h 1 nM or 100 nM tolcapone; 10 mu M of tolcapone, on the other hand, r esulted in a toxic effect on the cell aggregates. No differences in th e release of lactate dehydrogenase into the medium was observed in the aggregates treated with drugs as compared with the control cultures a fter 2 or 3 days post-ischemia.