Role of Hemoglobin and Iron in Hydrocephalus After Neonatal Intraventricular Hemorrhage
Neurosurgery - Current Issue
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. ABBREVIATIONS: aCSF, artificial cerebrospinal fluid DAB, 3,3′-diaminobenzidine-4HCl GMH-IVH, germinal matrix hemorrhage/intraventricular hemorrhage HO-1, heme oxygenase-1 ICH, intracerebral hemorrhage PBS, phosphate-buffered saline SVZ, subventricular zone TBST, tris-buffered saline with Tween 20Original Article: http://journals.lww.com/neurosurgery/Fulltext/2014/12000/Role_of_Hemoglobin_and_Iron_in_Hydrocephalus_After.20.aspx
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