Neurochemical changes in the rat occipital cortex and hippocampus after repetitive and profound hypoglycemia during the neonatal period: An Ex vivo 1H magnetic resonance spectroscopy study

摘要

The brain of a human neonate is more vulnerable to hypoglycemia than that of pediatric and adult patients. Repetitive and profound hypoglycemia during the neonatal period (RPHN) causes brain damage and leads to severe neurologic sequelae. Ex vivo high-resolution 1H nuclear magnetic resonance (NMR) spectroscopy was carried out in the present study to detect metabolite alterations in newborn and adolescent rats and investigate the effects of RPHN on their occipital cortex and hippocampus. Results showed that RPHN induces significant changes in a number of cerebral metabolites, and such changes are region-specific. Among the 16 metabolites detected by ex vivo 1H NMR, RPHN significantly increased the levels of creatine, glutamate, glutamine, γ-aminobutyric acid, and aspartate, as well as other metabolites, including succine, taurine, and myo-inositol, in the occipital cortex of neonatal rats compared with the control. By contrast, changes in these neurochemicals were not significant in the hippocampus of neonatal rats. When the rats had developed into adolescence, the changes above were maintained and the levels of other metabolites, including lactate, N-acetyl aspartate, alanine, choline, glycine, acetate, and ascorbate, increased in the occipital cortex. By contrast, most of these metabolites were reduced in the hippocampus. These metabolic changes suggest that complementary mechanisms exist between these two brain areas. RPHN appears to affect occipital cortex and hippocampal activities, neurotransmitter transition, energy metabolism, and other metabolic equilibria in newborn rats; these effects are further aggravated when the newborn rats develop into adolescence. Changes in the metabolism of neurotransmitter system may be an adaptive measure of the central nervous system in response to RPHN.