Brain Excitatory Amino Acid Concentrations Are Lower in the Neonatal Pig: A Buffer against Excitotoxicity?

Abstract

Hypoglycemic brain damage has been associated with high levels of the excitatory amino acids (EAA) aspartate and glutamate in the newborn and adult. We hypothesized that newborn piglet EAA would be different from those of older pigs when stressed with severe insulin-induced hypoglycemia (<30 mg/dl). Brain EAA were measured in piglets and adolescent pigs via microdialysis. Eleven of 12 newborn normoglycemic piglets had no detectable baseline levels (<0.5 µM) of EAA, while pigs had aspartate and glutamate concentrations of 1.78 ± 0.44 and 3.43 ± 1.14 µM (mean ± SEM), respectively. Piglet aspartate and glutamate concentrations reached but did not significantly exceed normoglycemic pig levels after 2 h with plasma glucose values ≤20 mg/ml. Elevations in EAA were only detected in piglets whose EEG activity ceased. Aspartate and glutamate concentrations did not increase in insulin-treated pigs nor in control animals. We speculate that newborns with blood glucose less than clinically acceptable values (35 mg/dl) may be protected from EAA-associated neuronal damage during acute hypoglycemia. Lower normoglycemic and hypoglycemic levels of EAA in newborns when compared to older pigs provide this protection.