COMPETING PROCESSES OF CELL-DEATH AND RECOVERY OF FUNCTION FOLLOWING ISCHEMIC PRECONDITIONING

The goal of the present study was to determine the neuroprotective eff icacy of ischemic preconditioning using behavioral, electrophysiologic al and histological endpoints at various time points up to 90 days pos tischemia. Gerbils were exposed to a brief, non-injurious episode of f orebrain ischemia (1.5 min) on each of 2 consecutive days. Three days following this preconditioning procedure, the animals received a 5 min occlusion. Other animals underwent sham surgery or a 5 min occlusion without preconditioning. Ischemic preconditioning appeared to provide striking histological protection at both rostral (similar to 80% and s imilar to 67% of sham) and posterior levels of hippocampus (similar to 94% and similar to 78% of sham) at 3 and 10 days survival, respective ly. However, in spite of the near normal number of CA1 neurons, animal s displayed marked impairments in an open field test of habituation as well as reduced dendritic field potentials in the CA1 area. Additiona lly, in ischemic animals the basal and apical dendritic regions of CA1 were nearly devoid of the cytoskeletal protein microtubule associated protein 2 (MAP2). Staining levels of MAP2 in preconditioned and sham animals were similar. With increasing survival time, open field behavi or as well as CA1 field potential amplitude recovered. Nonetheless, CA 1 cell death in ischemic preconditioned animals continued over the 90- day survival period (P < 0.05, vs. sham levels). Ischemic precondition ing provides a significant degree of neuroprotection characterized by a complex interplay of protracted cell death and neuroplasticity (reco very of function). These competing processes are best elucidated using a combination of functional and histological endpoints as well as mul tiple and extended survival times (i.e., greater than 7-10 days). (C) 1998 Elsevier Science B.V. All rights reserved.