Experiments in adult animals have indicated that hyperglycemia accentuates whereas hypoglycemia ameliorates hypoxic-ischemic brain damage. To determine whether hypoglycemia is protective or deleterious to the perinatal brain subjected to hypoxia-ischemia, 7-d postnatal rats were rendered hypoglycemic either by receiving an s.c. injection of insulin or fasting for 12 h. All rat pups underwent unilateral common carotid artery ligation followed by exposure to 8% oxygen-balance nitrogen at 37±C for 2 h. Control animals (no insulin or fasting) received s.c. injections of normal saline. Mean blood glucose concentrations were 5.4 ± 0.1, 4.3 ± 0.2, and 3.4 ± 0.1 mmol/L for control, insulin, and fasted animals, respectively. Blood β-hydroxy-butyrate concentrations were identical (0.5 ± 0.1 mmol/L) for control and insulin-treated animals, but more than doubled in concentration in the fasted animals (p p 1) insulin induced hypoglycemia does not provide a protective effect on perinatal hypoxic-ischemic brain damage, as in adults; and 2) fasting adequate to produce hypoglycemia and ketonemia improved neuropathologic outcome.
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