Deferoxamine alleviates chronic hydrocephalus after intraventricular hemorrhage through iron chelation and Wnt1/Wnt3a inhibition

Brain Res. 2015 Mar 30;1602:44-52. doi: 10.1016/j.brainres.2014.08.039. Epub 2014 Aug 22.

Abstract

Post-hemorrhagic chronic hydrocephalus (PHCH) is a common complication after intraventricular hemorrhage (IVH). The mechanism of PHCH is not fully understood, and its treatment is relatively difficult. In the present study, a rat model of PHCH was used to elucidate the role of iron in the pathogenesis of PHCH. The action of deferoxamine (DFX) in IVH-induced PHCH, the expression of brain ferritin, the concentration of iron in cerebrospinal fluid (CSF), and changes in Wnt1/Wnt3a gene expression were determined. Results indicate that iron plays an important role in the occurrence of hydrocephalus after IVH. The iron chelator, DFX, can decrease the concentrations of iron and ferritin after cerebral hemorrhage and can thereby decrease the incidence of hydrocephalus. In addition, after IVH, the gene expression of Wnt1 and Wnt3a was enhanced, with protein expression also upregulated; DFX was able to suppress both gene and protein expression of Wnt1 and Wnt3a in brain tissue. This indicates that iron may be the key stimulus that activates the Wnt signaling pathway and regulates subarachnoid fibrosis after cerebral hemorrhage, and that DFX may be a candidate for preventing PHCH in patients with IVH.

Keywords: Deferoxamine; Intraventricular hemorrhage; Iron chelation; Post-hemorrhagic chronic hydrocephalus; Wnt signaling pathway.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • Brain / drug effects*
  • Brain / pathology
  • Brain / physiopathology
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / drug therapy*
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Chronic Disease
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Ferritins / metabolism
  • Hydrocephalus / drug therapy*
  • Hydrocephalus / etiology
  • Hydrocephalus / pathology
  • Hydrocephalus / physiopathology
  • Immunohistochemistry
  • Iron / cerebrospinal fluid
  • Male
  • Maze Learning / drug effects
  • Maze Learning / physiology
  • Neuroprotective Agents / pharmacology*
  • Random Allocation
  • Rats, Sprague-Dawley
  • Reverse Transcriptase Polymerase Chain Reaction
  • Severity of Illness Index
  • Wnt1 Protein / metabolism
  • Wnt3A Protein / metabolism

Substances

  • Neuroprotective Agents
  • Wnt1 Protein
  • Wnt1 protein, rat
  • Wnt3A Protein
  • Ferritins
  • Iron
  • Deferoxamine