Abstract
We consider that the vulnerable and selective death of hippocampal CA1 neurons caused by short cessation of the brain circulation, might act like a fuse system in an electrical circuit, to save the whole brain and life from further ischemic insult. To test this hypothesis, we examined whether or not preconditioning by 5 min forebrain ischemia, which causes hippocampal CA1 neuronal death, could reduce the neuronal damage in other brain regions and decrease the mortality rate following 15 min forebrain ischemia in the gerbil. Male Mongolian gerbils were given either a single insult of 15 min forebrain ischemia by occlusion of the bilateral common carotid arteries (15 min group, n=61) or a double ischemic insult, i.e., 5 mm forebrain ischemia followed by 15 min forebrain ischemia 10 days later (5-15 min group, n=40). Gerbils were observed for 14 days after the last ischemic insult. 40% of the gerbils in the 15 min group survived, whereas significantly more gerbils (65%) in the 5-15 min group survived (p<0.05, Kaplan-Meier method). Furthermore, the 5-15 min group demonstrated a significantly reduced body weight loss after the last ischemic insult, as compared to the single insulted group (p<0.005). However, pathological analysis of brain tissues from 14-day survivors revealed that neuronal death in the surface layer of the cortex was more severe in the 5-15 min group than in the 15 min group, and severe neuronal death was present in the hippocampal CA3 region and the subiculum to the same extent. The present data indicate that preconditioning by 5 min forebrain ischemia can attenuate the mortality rate and body weight loss after 15 min forebrain ischemia. However, the potential protective role afforded by 5 min ischemia requires further detailed investigation.
