Role of Hemoglobin and Iron in hydrocephalus after neonatal intraventricular hemorrhage

Jennifer M. Strahle, Thomas Garton, Ahmad A. Bazzi, Harish Kilaru, Hugh J.L. Garton, Cormac O. Maher, Karin M. Muraszko, Richard F. Keep, Guohua Xi

Research output: Contribution to journalArticlepeer-review

54 Scopus citations

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. CONCLUSION: 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.

Original languageEnglish
Pages (from-to)696-705
Number of pages10
JournalNeurosurgery
Volume75
Issue number6
DOIs
StatePublished - 2014

Keywords

  • Hemoglobin
  • Hydrocephalus
  • Iron
  • Neonatal

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