Role of red blood cell lysis and iron in hydrocephalus after intraventricular hemorrhage

J Cereb Blood Flow Metab. 2014 Jun;34(6):1070-5. doi: 10.1038/jcbfm.2014.56. Epub 2014 Mar 26.


Thrombin and iron are two major players in intracerebral hemorrhage-induced brain injury and our recent study found that thrombin contributes to hydrocephalus development in a rat model of intraventricular hemorrhage (IVH). This study investigated the role of red blood cell (RBC) lysis and iron in hydrocephalus after IVH. There were three parts to this study. First, male Sprague-Dawley rats received an injection of saline, packed, or lysed RBCs into the right lateral ventricle. Second, rats had an intraventricular injection of iron or saline. Third, the rats received intraventricular injection of lysed RBCs mixed with deferoxamine (0.5 mg in 5 μL saline) or saline. All rats underwent magnetic resonance imaging at 24 hours and were then euthanized for brain edema measurement, western blot analysis, or brain histology. We found that intraventricular injection of lysed RBCs, but not packed RBCs, resulted in ventricular enlargement and marked increases in brain heme oxygenase-1 and ferritin at 24 hours. Intraventricular injection of iron also resulted in ventricular enlargement and ventricular wall damage 24 hours later. Coinjection of deferoxamine reduced lysed RBC-induced ventricular enlargement (P<0.01). These results suggest that iron, a degradation product of hemoglobin, has an important role in hydrocephalus development after IVH.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cerebral Hemorrhage / drug therapy
  • Cerebral Hemorrhage / metabolism*
  • Cerebral Hemorrhage / pathology
  • Deferoxamine / pharmacology
  • Erythrocytes*
  • Ferritins / metabolism
  • Heme Oxygenase-1 / biosynthesis
  • Hemolysis*
  • Hydrocephalus / diagnostic imaging
  • Hydrocephalus / drug therapy
  • Hydrocephalus / metabolism*
  • Hydrocephalus / pathology
  • Iron / metabolism*
  • Magnetic Resonance Imaging
  • Male
  • Radiography
  • Rats
  • Rats, Sprague-Dawley
  • Siderophores / pharmacology


  • Siderophores
  • Ferritins
  • Iron
  • Heme Oxygenase-1
  • Deferoxamine