Activation of caspase-3 in permanent and transient brain ischaemia in man

Animal studies have shown brain ischaemia to cause oxidative damage to DNA and activation of caspase-3, leading to apoptosis. These changes may be exa cerbated by reperfusion. To assess caspase-3 activation after transient and permanent brain ischaemia in man, we examined brain tissue from patients w ho had experienced a cardiac arrest with resuscitation or an atherothrombot ic brain infarct, and died 12 h to 9 days later. Sections were immunostaine d for activated caspase-3 or the 89kDa caspase-3-mediated cleavage product of poly(ADP-ribose) polymerase. Brain ischaemia caused activation of caspas e-3 in macrophages/microglia. Some neurons showed delayed activation of cas pase-3 after cardiac arrest, but very few in atherothrombotic infarcts. In man, activation of caspase-3 plays little part in neuronal death in atherot hrombotic infarcts but may contribute to delayed death of neurons after car diac arrest. NeuroReport 11:2495-2499 (C) 2000 Lippincott Williams & Wilkin s.