Critical values for plasma glucose in aggravating ischaemic brain damage: correlation to extracellular pH

The objective of the present experiments was to characterize conditions under which pre-ischaemic hyperglycaemia aggravates brain damage following transient forebrain ischaemia. Specifically, we wished to explore whether accentuated damage is a threshold function of plasma glucose concentration or pH, as assessed by measurements of extracellular pH (pHe). Forebrain ischaemia of 10 min duration was induced in rats at varying degrees of hyperglycaemia, with continuous measurements of pHe, and the animals were allowed to survive for 7 days before histopathological evaluation of the density and distribution of brain damage. Ischaemic brain damage appeared as a threshold function of plasma glucose concentration. At values of 4-6 mM virtually no damage was observed in any other structure than the CA1 sector of the hippocampus and, even in that structure, damage was variable. At glucose concentrations of 8-12 mM moderate damage was observed infrequently in caudoputamen, parietal cortex, and thalamus. At values above 12 mM, damage increased dramatically in these areas, and additional structures were recruited in the damage process (cingulate cortex, the CA3 sector of the hippocampus, and substantia nigra). Measurements of pHe in parietal cortex showed a threshold for seizure induction at values of 6.4-6.5, probably corresponding to intracellular pH values of 6.2-6.3. The threshold for aggravation of histopathological damage was similar. It is concluded that a moderate increase in plasma glucose in the threshold range predisposes the tissue to aggravated damage, probably by activating biochemical reactions or pathophysiological events with a steep pH dependence.