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.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08HD047276-02
Application #
6949918
Study Section
Pediatrics Subcommittee (CHHD)
Program Officer
Vitkovic, Ljubisa
Project Start
2004-09-15
Project End
2007-08-31
Budget Start
2005-09-01
Budget End
2006-08-31
Support Year
2
Fiscal Year
2005
Total Cost
$123,482
Indirect Cost
Name
University of Minnesota Twin Cities
Department
Pediatrics
Type
Schools of Medicine
DUNS #
555917996
City
Minneapolis
State
MN
Country
United States
Zip Code
55455
Rao, Raghavendra; Ennis, Kathleen; Mitchell, Eugena P et al. (2016) Recurrent Moderate Hypoglycemia Suppresses Brain-Derived Neurotrophic Factor Expression in the Prefrontal Cortex and Impairs Sensorimotor Gating in the Posthypoglycemic Period in Young Rats. Dev Neurosci 38:74-82
Rao, Anirudh R; Quach, Hung; Smith, Ed et al. (2014) Changes in ascorbate, glutathione and ?-tocopherol concentrations in the brain regions during normal development and moderate hypoglycemia in rats. Neurosci Lett 568:67-71
Ennis, Kathleen; Deelchand, Dinesh Kumar; Tkac, Ivan et al. (2011) Determination of oxidative glucose metabolism in vivo in the young rat brain using localized direct-detected ¹³C NMR spectroscopy. Neurochem Res 36:1962-8
Rao, Raghavendra; Ennis, Kathleen; Long, Jeffery D et al. (2010) Neurochemical changes in the developing rat hippocampus during prolonged hypoglycemia. J Neurochem 114:728-38
Rao, Raghavendra; Sperr, Dustin; Ennis, Kathleen et al. (2009) Postnatal age influences hypoglycemia-induced poly(ADP-ribose) polymerase-1 activation in the brain regions of rats. Pediatr Res 66:642-7
Raman, Lakshmi; Hamilton, Kathryn L; Gewirtz, Jonathan C et al. (2008) Effects of chronic hypoxia in developing rats on dendritic morphology of the CA1 subarea of the hippocampus and on fear-potentiated startle. Brain Res 1190:167-74
Ennis, Kathleen; Tran, Phu V; Seaquist, Elizabeth R et al. (2008) Postnatal age influences hypoglycemia-induced neuronal injury in the rat brain. Brain Res 1224:119-26
Terpstra, Melissa; Tkac, Ivan; Rao, Raghavendra et al. (2006) Quantification of vitamin C in the rat brain in vivo using short echo-time 1H MRS. Magn Reson Med 55:979-83
Raman, Lakshmi; Georgieff, Michael K; Rao, Raghavendra (2006) The role of chronic hypoxia in the development of neurocognitive abnormalities in preterm infants with bronchopulmonary dysplasia. Dev Sci 9:359-67