Preischemic Hyperglycemia Enhances Postischemic Depression of Cerebral Metabolic Rate

The objective of the present study was to explore metabolic correlates to the appearance of postischemic seizures and the enhancement of brain damage observed in subjects that are made hyperglycemic prior to the induction of ischemia. To that end, transient forebrain ischemia of 10-min duration was induced in normo- and hyperglycemic rats, with subsequent measurements of local CMR glc (LCMR glc ) after 3,6,12, and 18 h of recirculation. We posed the questions of whether postischemic depression of LCMR glc is exaggerated by preischemic hyperglycemia and whether there are signs of localized increases in LCMR glc in hyperglycemic rats, reflecting subclinical seizure activity. The results confirmed the presence of a long-lasting postischemic depression of LCMR glc in normoglycemic rats. This depression was partially but not tightly related to the degree of reduction of local CBF during ischemia. The depression was most pronounced in neocortical areas and in the hippocampus, but notably it was less pronounced in the densely ischemic caudoputamen. Little or no reduction of LCMR glc was observed in moderately or mildly ischemic structures such as the hypothalamus, red nucleus, and cerebellum. Preischemic hyperglycemia markedly accentuated the postischemic depression of LCMR glc . For example, although the subjects quickly regained wakefulness and motility, they had LCMR glc values in neocortical areas that remained below 50% of control. Corresponding but quantitatively less pronounced reductions in LCMR glc were observed in other areas. Notably, preischemic hyperglycemia reduced postischemic LCMR glc also in areas that showed only moderate to mild reductions in CBF during the ischemia. The results thus demonstrate that preischemic hyperglycemia has pronounced metabolic effects in the postischemic recovery period. The data provide no indication that postischemic seizures, which develop after a recovery period of ∼24 h, are preceded by the appearance of hypermetabolic “seizure” foci.