Effect of hyperglycemia on brain cell membrane function and energy metabolism during hypoxia–ischemia in newborn piglets

Abstract

The purpose of this study was to test the hypothesis that hyperglycemia ameliorates changes in brain cell membrane function and preserves cerebral high energy phosphates during hypoxia–ischemia in newborn piglets. A total of 42 ventilated piglets were divided into 4 groups, normoglycemic/normoxic(group 1, n=9), hyperglycemic/normoxic(group 2, n=8), normoglycemic/hypoxic–ischemic(group 3, n=13) and hyperglycemic/hypoxic–ischemic(group 4, n=12) group. Cerebral hypoxia–ischemia was induced by occlusion of bilateral common carotid arteries and simultaneous breathing with 8% oxygen for 30 min. Hyperglycemia (blood glucose 350–400 mg/dl) was maintained for 90 min before and throughout hypoxia–ischemia using modified glucose clamp technique. Changes in cytochrome aa3 were continuously monitored using near infrared spectroscopy. Blood and CSF glucose and lactate were monitored. Na +, K +-ATPase activity, lipid peroxidation products (conjugated dienes), tissue high energy phosphates (ATP and phosphocreatine) levels and brain glucose and lactate levels were determined biochemically in the cerebral cortex. During hypoxia–ischemia, glucose levels in blood and CSF were significantly elevated in hyperglycemic/hypoxic–ischemic group compared with normoglycemic/hypoxic–ischemic group, but lactate levels in blood and CSF were not different between two groups. At the end of hypoxia–ischemia of group 3 and 4, ▵ Cyt aa3, Na +, K +-ATPase activity, ATP and phosphocreatine values in brain were significantly decreased compared with normoxic groups 1 and 2, but were not different between groups 3 and 4. Levels of conjugated dienes and brain lactate were significantly increased in groups 3 and 4 compared with groups 1 and 2, and were significantly elevated in group 4 than in group 3 (0.30±0.11 vs. 0.09±0.02 μmol g −1 protein, 26.4±7.6 vs. 13.1±2.6 mmol kg −1, p<0.05). These findings suggest that hyperglycemia does not reduce the changes in brain cell membrane function and does not preserve cerebral high energy phosphates during hypoxia–ischemia in newborn piglets. We speculate that hyperglycemia may be harmful during hypoxia–ischemia due to increased levels of lipid peroxidation in newborn piglet.