title: Perinatal iron deficiency predisposes the developing rat hippocampus to greater injury from mild to moderate hypoxia-ischemia.
abstract: The hippocampus is injured in both hypoxia-ischemia (HI) and perinatal iron deficiency that are co-morbidities in infants of diabetic mothers and intrauterine growth restricted infants. We hypothesized that preexisting perinatal iron deficiency predisposes the hippocampus to greater injury when exposed to a relatively mild HI injury. Iron-sufficient and iron-deficient rats (hematocrit 40% lower and brain iron concentration 55% lower) were subjected to unilateral HI injury of 15, 30, or 45 mins (n=12 to 13/HI duration) on postnatal day 14. Sixteen metabolite concentrations were measured from an 11 microL volume on the ipsilateral (HI) and contralateral (control) hippocampi 1 week later using in vivo 1H NMR spectroscopy. The concentrations of creatine, glutamate, myo-inositol, and N-acetylaspartate were lower on the control side in the iron-deficient group (P<0.02, each). Magnetic resonance imaging showed hippocampal injury in the majority of the iron-deficient rats (58% versus 11%, P<0.0001) with worsening severity with increasing durations of HI (P=0.0001). Glucose, glutamate, N-acetylaspartate, and taurine concentrations were decreased and glutamine, lactate and myo-inositol concentrations, and glutamine/glutamate ratio were increased on the HI side in the iron-deficient group (P<0.01, each), mainly in the 30 and 45 mins HI subgroups (P<0.02, each). These neurochemical changes likely reflect the histochemically detected neuronal injury and reactive astrocytosis in the iron-deficient group and suggest that perinatal iron deficiency predisposes the hippocampus to greater injury from exposure to a relatively mild HI insult.
authors.affiliation: Department of Pediatrics, University of Minnesota, Minneapolis, Minnesota 55455, USA. raoxx017@umn.edu
authors.forename: Raghavendra
authors.initials: R
authors.lastname: Rao
authors.forename: Ivan
authors.initials: I
authors.lastname: Tkac
authors.forename: Elise L
authors.initials: EL
authors.lastname: Townsend
authors.forename: Kathleen
authors.initials: K
authors.lastname: Ennis
authors.forename: Rolf
authors.initials: R
authors.lastname: Gruetter
authors.forename: Michael K
authors.initials: MK
authors.lastname: Georgieff
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001253:Astrocytes / Q000473:pathology; D001835:Body Weight / Q000502:physiology; D001923:Brain Chemistry; D004574:Electromagnetic Fields; D005260:Female; D006624:Hippocampus / Q000254:growth & development* / Q000473:pathology*; D006651:Histocytochemistry; D020925:Hypoxia-Ischemia, Brain / Q000473:pathology*; D007501:Iron / Q000378:metabolism; D000090463:Iron Deficiencies; D008279:Magnetic Resonance Imaging; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009474:Neurons / Q000473:pathology; D009929:Organ Size / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D007501:Iron