Factors Influencing the Frequency of Fluorescence Transients as Markers of Peri-Infarct Depolarizations in Focal Cerebral Ischemia

Abstract

Background and Purpose —Peri-infarct depolarizations (PIDs) that occur in ischemic boundary zones of the cerebral cortex of experimental animals have been shown to promote rather than simply to indicate the evolution of the lesion and are especially prominent in the rat. To study the influence of one factor, species, on PID incidence, we compared the frequency of PIDs in a primate species, the squirrel monkey, with that in the cat after middle cerebral artery occlusion. Plasma glucose was reviewed as a possible cause of interexperiment variability in the cat experiments. Methods —In open-skull experiments under chloralose anesthesia, changes in cortical fluorescence believed to indicate NADH/NAD + redox state, as markers of PIDs, were recorded by serial imaging of the cortical surface in vivo for 4 hours after middle cerebral artery occlusion. Results —Fluorescence transients occurred in squirrel monkeys at a frequency (mean±SD) of 0.7±0.8 hours −1 (n=5), which was not significantly less than in that observed in cats (1.3±1.6 hours −1 , n=8). Data from the cat experiments indicated a relationship between number of transients (dependent) and plasma glucose, with a striking increase in PID frequency in association with values of mean postocclusion plasma glucose <4.1 mmol/L (Mann-Whitney U =15.0, P =0.034); this observation agrees well with other published findings. Conclusions —Transient changes in fluorescence strongly suggestive of peri-infarct depolarizations, either transient or terminal, occur and propagate in the ischemic cerebral cortex of a nonhuman primate. The results also suggest that the relationship of frequency of peri-infarct depolarizations with plasma glucose requires further examination, to confirm the finding and to determine a safe lower limit for a target range for control of plasma glucose if insulin is used in the management of patients with cerebral ischemia.