title: Role of hemoglobin and iron in hydrocephalus after neonatal intraventricular hemorrhage.
abstract: BACKGROUND
  Neonatal germinal matrix hemorrhage/intraventricular hemorrhage is common and often results in hydrocephalus. The pathogenesis of posthemorrhagic hydrocephalus is not fully understood.
  
  
  OBJECTIVE
  To explore the potential role of hemoglobin and iron released after hemorrhage.
  
  
  METHODS
  Artificial cerebrospinal fluid (aCSF), hemoglobin, or iron was injected into the right lateral ventricle of postnatal day-7 Sprague Dawley rats. Ventricle size, heme oxygenase-1 (HO-1) expression, and the presence of iron were evaluated 24 and 72 hours after injection. A subset of animals was treated with an iron chelator (deferoxamine) or vehicle for 24 hours after hemoglobin injection, and ventricle size and cell death were evaluated.
  
  
  RESULTS
  Intraventricular injection of hemoglobin and iron resulted in ventricular enlargement at 24 hours compared with the injection of aCSF. Protoporphyrin IX, the iron-deficient immediate heme precursor, did not result in ventricular enlargement after injection into the ventricle. HO-1, the enzyme that releases iron from heme, was increased in the hippocampus and cortex of hemoglobin-injected animals at 24 hours compared with aCSF-injected controls. Treatment with an iron chelator, deferoxamine, decreased hemoglobin-induced ventricular enlargement and cell death.
  
  
  CONCLUSIONS
  Intraventricular injection of hemoglobin and iron can induce hydrocephalus. Treatment with an iron chelator reduced hemoglobin-induced ventricular enlargement. This has implications for the pathogenesis and treatment of posthemorrhagic hydrocephalus.
  
  
  BACKGROUND
  aCSF, artificial cerebrospinal fluidDAB, 3,3'-diaminobenzidine-4HClGMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhageHO-1, heme oxygenase-1ICH, intracerebral hemorrhagePBS, phosphate-buffered salineSVZ, subventricular zoneTBST, tris-buffered saline with Tween 20.
authors.affiliation: Department of Neurosurgery, University of Michigan, Ann Arbor, Michigan.
authors.forename: Jennifer M
authors.initials: JM
authors.lastname: Strahle
authors.forename: Thomas
authors.initials: T
authors.lastname: Garton
authors.forename: Ahmad A
authors.initials: AA
authors.lastname: Bazzi
authors.forename: Harish
authors.initials: H
authors.lastname: Kilaru
authors.forename: Hugh J L
authors.initials: HJ
authors.lastname: Garton
authors.forename: Cormac O
authors.initials: CO
authors.lastname: Maher
authors.forename: Karin M
authors.initials: KM
authors.lastname: Muraszko
authors.forename: Richard F
authors.initials: RF
authors.lastname: Keep
authors.forename: Guohua
authors.initials: G
authors.lastname: Xi
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D015153:Blotting, Western; D002543:Cerebral Hemorrhage / Q000150:complications* / Q000378:metabolism / Q000503:physiopathology; D003676:Deferoxamine / Q000494:pharmacology; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000032:analysis / Q000096:biosynthesis; D006454:Hemoglobins / Q000008:administration & dosage / Q000633:toxicity*; D006849:Hydrocephalus / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007501:Iron / Q000008:administration & dosage / Q000633:toxicity*; D020547:Lateral Ventricles / Q000473:pathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D006454:Hemoglobins; D007501:Iron; D051547:Heme Oxygenase-1; D003676:Deferoxamine