Phlebotomy-induced anemia alters hippocampal neurochemistry in neonatal mice

Diana J. Wallin, Ivan Tkac, Sara Stucker, Kathleen M. Ennis, Martha Sola-Visner, Raghavendra Rao, Michael K. Georgieff

Research output: Contribution to journalArticlepeer-review

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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.Conclusion: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.

Original languageEnglish (US)
Pages (from-to)765-771
Number of pages7
JournalPediatric Research
Issue number6
StatePublished - Jun 26 2015

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Publisher Copyright:
Copyright © 2015 International Pediatric Research Foundation, Inc.


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