Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice.
BACKGROUND
Phlebotomy-induced anemia (PIA) is common in preterm infants. The hippocampus undergoes rapid differentiation during late fetal/early neonatal life and relies on adequate oxygen and iron to support oxidative metabolism necessary for development. Anemia shortchanges these two critical substrates, potentially altering hippocampal development and function.


METHODS
PIA (hematocrit <25%) was induced in neonatal mice pups from postnatal day (P)3 to P14. Neurochemical concentrations in the hippocampus were determined using in vivo (1)H NMR spectroscopy at 9.4T and compared with control animals at P14. Gene expression was assessed using quantitative real-time polymerase chain reaction (qRT-PCR).


RESULTS
PIA decreased brain iron concentration, increased hippocampal lactate and creatine concentrations, and decreased phosphoethanolamine (PE) concentration and the phosphocreatine/creatine ratio. Hippocampal transferrin receptor (Tfrc) gene expression was increased, while the expression of calcium/calmodulin-dependent protein kinase type IIα (CamKIIα) was decreased in PIA mice.


CONCLUSIONS
This clinically relevant model of neonatal anemia alters hippocampal energy and phospholipid metabolism and gene expression during a critical developmental period. Low target hematocrits for preterm neonates in the neonatal intensive care unit (NICU) may have potential adverse neural implications.
1] Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota [2] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Diana J
DJ
Wallin
Center for Magnetic Resonance Research, Department of Radiology, University of Minnesota, Minneapolis, Minnesota.
Ivan
0000000150540150
I
Tkac
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Sara
S
Stucker
Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Kathleen M
KM
Ennis
Division of Newborn Medicine, Boston Children's Hospital and Department of Medicine, Harvard Medical School, Boston, Massachusetts.
Martha
M
Sola-Visner
1] Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota [2] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Raghavendra
R
Rao
1] Graduate Program in Neuroscience, University of Minnesota, Minneapolis, Minnesota [2] Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota.
Michael K
MK
Georgieff
D000740:Anemia / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D000831:Animals, Newborn; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000502:physiology*; D006400:Hematocrit; D006624:Hippocampus / Q000737:chemistry*; D007501:Iron / Q000378:metabolism; D009682:Magnetic Resonance Spectroscopy; D051379:Mice; D018962:Phlebotomy; D060888:Real-Time Polymerase Chain Reaction
D007501:Iron