PROTECTIVE EFFECT OF APOPTOSIS-INHIBITORY AGENT, N-TOSYL-L-PHENYLALANYL CHLOROMETHYL KETONE AGAINST ISCHEMIA-INDUCED HIPPOCAMPAL NEURONAL DAMAGE

Delayed neuronal death in the gerbil hippocampal CA1 sector occurs 48 to 72 hours after severe forebrain ischemia. DNA fragmentation is obse rved in the hippocampal CA1 neurons at around that time. We show here that an inhibitor of proteolytic process of apoptosis, N-tosyl-L-pheny lalanyl chloromethyl ketone (TPCK), protected hippocampal neuronal dam age by inhibition of the DNA fragmentation in a dose-dependent manner and that TPCK induced an apoptosis-regulating molecule, Bcl-2 protein, in the surviving neurons. These results suggest the prevention of apo ptosis-related DNA fragmentation by TPCK may be an attractive therapeu tic strategy for preserving hippocampal neurons from ischemic insult.