The candidate is a neonatologist at the University of Minnesota. His long-term goal is to pursue an academic career devoted to basic research. The candidate encountered malnutrition in infants and children during his medical training. This experience made him interested in the mechanistic aspects of early nutritional deficiencies on brain development. During his fellowship, the candidate studied the effects of perinatal iron deficiency on the developing brain using histochemical approaches. The proposed application will provide him the additional training necessary to transition to independent research. Under the guidance of his mentor, the candidate will study substrate utilization in the developing brain using high-field 1H and 13C NMR spectroscopy. He will use acute hypoglycemia as a model to become trained in these novel in vivo methods. Hypoglycemia during the neonatal period has been associated with long-term neurological deficits. Therapeutic interventions, based on blood glucose measurements, have been proposed to prevent these deficits. An in vivo evaluation of substrate preference and utilization, specifically those of glucose, ketone bodies, and brain glycogen, during hypoglycemia is essential to optimize therapeutic interventions for neonatal hypoglycemia. High-field 1H and 13C NMR spectroscopy are excellent methods to study substrate delivery and metabolism in vivo in the brain. Using these methods, the candidate will pursue, in Specific Aim 1, to characterize the cerebral transport and utilization of glucose and alternate energy substrates in the typically developing brain;
in Specific Aim 2, to characterize the neuroprotective roles of the alternate substrates and brain glycogen during hypoglycemia in the developing brain; and in Specific Aim 3, to characterize the acute neurochemical changes and the long-term neurological sequelae of graded hypoglycemia in the developing brain.
