Preischemic Hyperglycemia Enhances Postischemic Depression of Cerebral Metabolic Rate

Abstract

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 CMRglc (LCMRglc) after 3, 6, 12, and 18 h of recirculation. We posed the questions of whether postischemic depression of LCMRglc is exaggerated by preischemic hyperglycemia and whether there are signs of localized increases in LCMRglc in hyperglycemic rats, reflecting subclinical seizure activity. The results confirmed the presence of a long-lasting postischemic depression of LCMRglc 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 LCMRglc was observed in moderately or mildly ischemic structures such as the hypothalamus, red nucleus, and cerebellum. Preischemic hyperglycemia markedly accentuated the postischemic depression of LCMRglc. For example, although the subjects quickly regained wakefulness and motility, they had LCMRglc values in neocortical areas that remained below 50% of control. Corresponding but quantitatively less pronounced reductions in LCMRglc were observed in other areas. Notably, preischemic hyperglycemia reduced postischemic LCMRglc 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 approximately 24 h, are preceded by the appearance of hypermetabolic "seizure" foci.

Carbohydrate and Energy Metabolism during the Evolution of Hypoxic-Ischemic Brain Damage in the Immature Rat

“…The depression of glucose utilization at this interval was most likely a reflec tion of underlying brain damage, which is well advanced at this stage in its evolution (Rice et al, 1981). The biochemical mechanism underlying the reduction in metabolism remains unclear but may relate to the post-hypoxic-ischemic accumulation (or loss) of metabolic byproducts known to inhibit (or accelerate) glycolytic flux (Levy and Duffy, 1977;Pulsinelli et al, 1982a;Tanaka et al, 1985;Kozuka et al, 1989). Whatever the mechanism, de pressed oxidative consumption of glucose would limit the production of reducing equivalents via the tricarboxylic acid (Krebs) cycle, thereby con tributing to the incomplete resynthesis of ATP (see above) (Welsh et al, 1982a).…”

Time Course of Hippocampal Glucose Utilization and Persistence of Parvalbumin Immunoreactive Neurons after Ibotenic Acid—Induced Lesions of the Rat Dentate Area

“…After transient cerebral ischemia, the common findings seem to be that days to weeks after the ischemic insult, LCGU increases in the CAl sector and decreases in most other hip pocampal structures, while months after ischemia LCG U is reduced in all hippocampal areas (Diemer and Siemkowicz, 1980;Pulsinelli et aI., 1982;lzu miyama et a\. , 1987;Kozuka et a\. , 1989;Beck et a\., 1990aBeck et a\., , 1990bRischke and Krieglstein, 1991).…”

Evolving Concepts About the Role of Acidosis in Ischemic Neuropathology

“…In vivo, preischemic hyperglycemia is known to potentiate the postischemic depression of cerebral metabolism in both rodents and humans, possibly due to enhanced acidosis (Welsh et al, 1983;Kozuka et al, 1989;Kushner et al, 1990). Such metabolic depression has traditionally been viewed as detrimental to neuronal cells in the context of ischemia.…”

“…1). Both barbiturates and hypothermia also significantly depress neuronal metabolism (see Siesjo, 1978) and both have been used to antagonize ischemic neuronal injury (Paschen et al, 1988; Busto et al, 1989;Freund et al, 1990; Mitani and Kataoka, 199 l), although barbiturates appear to be less consistent than hypothermia in mediating neuroprotection.In vivo, preischemic hyperglycemia is known to potentiate the postischemic depression of cerebral metabolism in both rodents and humans, possibly due to enhanced acidosis (Welsh et al, 1983;Kozuka et al, 1989;Kushner et al, 1990). Such metabolic depression has traditionally been viewed as detrimental to neuronal cells in the context of ischemia.…”