NEITHER MODERATE HYPOXIA NOR MILD HYPOGLYCEMIA ALONE CAUSES ANY SIGNIFICANT INCREASE IN CEREBRAL [CA2+](I) - ONLY A COMBINATION OF THE 2 INSULTS HAS THIS EFFECT - A P-31 AND F-19 NMR-STUDY

(1) The energy state and free intracellular calcium concentration ([Ca2+]i) of superfused cortical slices were measured in moderate hypoxia (approximately 65 muM 02), in mild hypoglycaemia (0.5 mM glucose), and in combinations of the two insults using F-19 and P-31 NMR spectroscopy. (2) Neither hypoxia nor hypoglycaemia alone caused any significant change in [Ca2+]i. Hypoxia caused a 400/o fall in phosphocreatine (PCr) content but not in ATP level, and hypoglycaemia produced a slight fall in both (as expected from previous studies). These changes in the energy state recovered on return to control conditions. (3) A combined sequential insult (hypoxia, followed by hypoxia plus hypoglycaemia) produced a 100% increase in [Ca2+], and a decrease in PCr level to approximately 25% of control. The reverse combined sequential insult (hypoglycaemia, followed by hypoglycaemia plus hypoxia) had the same effect. On return to control conditions there was some decrease in [Ca2+], and a small increase in PCr content, but neither recovered to control levels. (4) Exposure of the tissue to the combined simultaneous insult (hypoxia plus hypoglycaemia) immediately after the control spectra had been recorded resulted in a fivefold increase in [Ca2+]i and a similar decrease in PCr level to 20-25% of control. There was little if any change of [Ca2+]i or PCr level on return to control conditions. (5) These results are discussed in terms of metabolic adaptation of some but not all of the cortical cells to the single type of insult, which renders the tissues less vulnerable to the combined insult.