Our research focus is energy metabolism, injury and neuroprotection in the developing brain. We investigate the effects of early-life iron deficiency, perinatal dysglycemia and hypoxia-ischemia in rodent and nonhuman primate models using ultra-high-field in vivo MR spectroscopy, molecular and histochemical analyses, and proteomic and metabolomic analyses of biofluids. Our studies are designed to increase knowledge on the role of substrate delivery for optimal brain metabolism, delineate the pathways of brain injury and neuroprotection, and develop neuroprotection strategies using this information.
A major focus of our research is biomarker discovery using proteomic and metabolomic analyses of paired plasma and CSF samples from nonhuman primate infants with early-life iron deficiency. Early-life iron deficiency anemia is associated with long-term neurodevelopmental impairments that fail to respond to iron treatment. Our goal is to discover plasma biomarkers of impending brain dysfunction in the preanemic period that can be used for early treatment of iron deficiency in human infants. This is a collaborative project with researchers from University of Wisconsin-Madison.
Our second goal is to develop novel therapeutic strategies for promoting normal brain development in adverse perinatal conditions. In this area, we are investigating umbilical cord stem cell transfusion as treatment for intraventricular hemorrhage in preterm infants, and intranasal insulin administration as treatment for neonatal hyperglycemia and perinatal iron deficiency in animal models. We collaborate with researchers from the Departments of Pediatrics, Cell Therapeutics, Neurosurgery, Psychology and the Center for Magnetic Resonance Research at the University of Minnesota, and Alzheimer's Research Center at Regions Hospital in St. Paul in these studies.
(For a comprehensive list of recent publications, refer to PubMed, a service provided by the National Library of Medicine.)
- Satrom KM, Ennis K, Sweis BM, Matveeva TM, Chen J, Hanson L, Maheshwari A, Rao R. Neonatal hyperglycemia induces CXCL10/CXCR3 signaling and microglial activation and impairs long-term synaptogenesis in the hippocampus and alters behavior in rats. J Neuroinflammation. 2018 Mar 15;15(1):82. PMID 29544513
- Rao R, Nashawaty M, Fatima S, Ennis K, Tkac I. Neonatal hyperglycemia alters the neurochemical profile, dendritic arborization and gene expression in the developing rat hippocampus. NMR Biomed. 2018 Mar 13;. PMID: 29532970
- Cusick SE, Georgieff MK, Rao R. Approaches for Reducing the Risk of Early-Life Iron Deficiency-Induced Brain Dysfunction in Children. Nutrients. 2018 Feb 17;10(2). PMID: 29462970
- Rao R, Ennis K, Lubach GR, Lock EF, Georgieff MK, Coe CL. Metabolomic analysis of CSF indicates brain metabolic impairment precedes hematological indices of anemia in the iron-deficient infant monkey. Nutr Neurosci. 2018;21(1):40-48.
- Ennis K, Lusczek E, Rao R. Characterization of the concurrent metabolic changes in brain and plasma during insulin-induced moderate hypoglycemia using 1H NMR spectroscopy in juvenile rats. Neurosci Lett. 2017;653:370-375.
- Rao R, Ennis K, Mitchell EP, Tran PV, Gewirtz JC. 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. 2016;38(1):74-82
- Scheurer JM, Gray HL, Demerath EW, Rao R, Ramel SE. Diminished growth and lower adiposity in hyperglycemic very low birth weight neonates at 4 months corrected age. J Perinatol. 2016;36:145-50.
- Wallin DJ, Tkac I, Stucker S, Ennis KM, Sola-Visner M, Rao R, Georgieff MK. Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice. Pediatr Res. 2015;77(6):765-71.
- Maliszewski-Hall AM, Alexander M, Ivan Tkáč I, Öz G, Rao R. Differential effects of intrauterine growth restriction on the regional neurochemical profile of the developing rat brain. Neurochem Res. 2017;42(1):133-140.
- Rao R Hypothalamic-pituitary-adrenal axis programming after recurrent hypoglycemia during development. J Clin Med. 2015;4(9):1729-40.
- Gisslen T, Varda B, Ennis K, Rao R. Recurrent hyperglycemia is associated with oxidative stress and microglial activation in the cerebral cortex of developing rats. Pediatr Res. 2015;78(5):513-9.
- Bora R, Akhtar S, Venkatasubramaniam, Wolfson J, Rao R. Effect of long umbilical cord milking on hemoglobin and serum ferritin at six months in full-term infants of anemic and non-anemic mothers. J Perinatol. 2015;35(10):832-6.
- Chouthai NS, Sobczek H, Khan R, Subramanian D, Raman S, Rao R. Hyperglycemia is associated with poor outcome in newborn infants undergoing therapeutic hypothermia for hypoxic ischemic encephalopathy. J Neonatal Perinatal Med. 2015;8(2):125-31.
- Maliszewski-Hall A, Stein A, Alexander M, Rao R. Acute hypoglycemia results in reduced cortical neuronal injury in the developing IUGR rat. Pediatr Res. 2015;78(1):7-13.
- Wallin DJ, Tkac I, Stucker S, Ennis K, Rao R, Georgieff MK. Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice. Pediatr Res 2015;77:765-71.
- Ennis K, Dotterman H, Stein A, Rao R. Hyperglycemia accentuates and ketonemia attenuates hypoglycemia-induced neuronal injury in the developing rat brain. Pediatr Res. 2015;77:84-90.
- Rao AR, Quach H, Smith E, Vatassery GT, Rao R. Changes in ascorbate, glutathione and α-tocopherol concentrations in the brain regions during normal development and moderate hypoglycemia in rats. Neurosci Lett. 2014;568:67-71.
- Rao R, Tkac I, Unger EL, Ennis K, Hurst A, Schallert T, Connor J, Felt B, Georgieff MK. Iron supplementation dose for perinatal iron deficiency differentially alters the neurochemistry of the frontal cortex and hippocampus in adult rats. Pediatr Res. 2013;73(1):31-7.
- Shao J, Lou J, Rao R, Georgieff MK, Kaciroti N, Felt B, Zhao Z-Y, Lozoff B. Maternal serum ferritin concentration is positively associated with newborn iron stores in women with low ferritin status in late pregnancy. J Nutr. 2012;142:2004–2009.
- Unger EL, Hurst AR, Georgieff MK, Schallert T, Rao R, Connor J, Kaciroti N, Lozoff B, Felt B. Behavior and monoamine deficits in pre- and perinatal iron deficiency are not corrected by early postnatal moderate or high iron diet in rats. J Nutr. 2012;142(11):2040-9
- Traudt CM, Tkac I, Ennis KM, Sutton LM, Mammel DM, Rao R. Postnatal morphine administration alters hippocampal development in rats. J Neurosci Res. 2012;90(1):307-14.
- Schmidt AT, Alvarez GC, Grove WM, Rao R, Georgieff MK. Early iron deficiency enhances stimulus-response learning of adult rats in the context of competing spatial information. Develop Cogn Neurosci 2012;2:174-180.