Rasagiline, a monoamine oxidase‐B inhibitor, protects NGF‐differentiated PC12 cells against oxygen‐glucose deprivation

In our in vitro model, rasagiline a selective irreversible monoamine oxidase‐B (MAO‐B) inhibitor, protected nerve growth factor (NGF)‐differentiated PC12 cells from cell death under oxygen and glucose deprivation (OGD). The severity of the OGD insult, as expressed by cell death, was time‐dependent. Exposure of the cells to OGD for 3 hr followed by 18 hr of reoxygenation caused about 30–40% cell death. Under these conditions, the neuroprotective effect of rasagiline was dose‐dependent: rasagiline reducing OGD‐induced cell death by 68% and 80% at 100 nM and 1 μM, respectively. The neuroprotective effect of rasagiline was also observed when added after the OGD insult (55% reduction in cell death). Under rasagiline treatment, there was a lesser decrease in ATP content in cultures exposed to OGD compared with that in untreated cultures. OGD followed by reoxygenation resulted in a several fold increase in PGE 2 release into the extracellular medium. Rasagiline (100 nM–1 μM) markedly inhibited OGD‐induced PGE 2 release. Clorgyline, a monoamine oxidase‐A (MAO‐A) inhibitor, did not protect NGF‐differentiated PC12 cells against OGD‐induced cell death. As NGF‐differentiated PC12 cells contain exclusively MAO type A, these data suggest that the neuroprotective effect of rasagiline under OGD conditions is independent of MAO inhibition. J. Neurosci. Res. 58:456–463, 1999. © 1999 Wiley‐Liss, Inc.