SPATIOTEMPORAL RELATIONSHIP OF APOPTOTIC CELL-DEATH TO LYMPHOMONOCYTIC INFILTRATION IN PHOTOCHEMICALLY INDUCED FOCAL ISCHEMIA OF THE RAT CEREBRAL-CORTEX

In this study we examined the time course of apoptotic cell death afte r photochemically induced focal ischemia of the rat cerebral cortex. F or unequivocal differentiation between apoptosis and necrosis two crit eria of programmed cell death were used: terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end labeling (TUNEL) and m orphological evidence of fragmentation and marginalization of nuclei. After photothrombosis, many TUNEL-positive cells were found within the infarct region from 12 h to 3 days. By day 6 they were preferentially located in the boundary zone of the infarct, and by day 14 they had d isappeared. A high proportion of TUNEL-positive cells displayed fragme ntation or marginalization of their nuclei, indicating apoptosis. Neur ons, but not T cells and macrophages, were apoptotic. Inflammatory inf iltrates were in close contact to apoptotic neurons throughout the inf arct areas at day 1 and in the boundary zone between days 2 and 6 afte r photothrombosis. In summary, our study shows that neuronal apoptosis after cerebral ischemia is a prolonged process to which leukocyte-der ived cytokines may contribute. In contrast to autoimmune diseases of t he nervous system, termination of the local inflammatory response afte r cerebral ischemia does not involve apoptosis.