Deferoxamine reduces early brain injury following subarachnoid hemorrhage

Acta Neurochir Suppl. 2011;112:101-6. doi: 10.1007/978-3-7091-0661-7_18.

Abstract

The effect of subarachnoid hemoglobin on neuroglial cells contributing to early brain injury is unclear. Several intracerebral hemorrhage studies indicated that pathological iron deposition in the brain contributes to secondary brain injury. Therefore, the purpose of this study was to investigate the relationship between iron and neuroglial cell changes following SAH, and examine the effect of deferoxamine (DFX). SAH was induced in male Sprague-Dawley rats (n = 56) using an endovascular perforation technique. Animals were treated with DFX (100 mg/kg) or vehicle for 3 days. Rats were sacrificed at 6 h, days 1 and 3 to determine non-heme iron and heme oxygenase (HO)-1 expression using Western blot and immunohistochemistry analysis. To assess neuronal cell death, Fluoro-Jade- and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling (TUNEL) stainings were performed. Marked HO-1 upregulation at day 3 (P < 0.01) was accompanied by elevated non-heme iron (P < 0.01) and ferritin levels (P < 0.01). DFX treatment reduced brain non-heme iron concentration, ferritin expression and neuronal cell death at day 3 (P < 0.01) following SAH. These results suggest that excessive hemoglobin and iron overload play an important role in early brain injury following SAH. Acute treatment with DFX significantly ameliorates neuronal cell death and may be a potential therapeutic agent for SAH.

MeSH terms

  • Analysis of Variance
  • Animals
  • Brain / drug effects
  • Brain / metabolism
  • Brain Injuries / drug therapy*
  • Brain Injuries / etiology*
  • Brain Injuries / mortality
  • Brain Injuries / pathology
  • DNA Damage
  • Deferoxamine / therapeutic use*
  • Disease Models, Animal
  • Gene Expression Regulation / drug effects
  • Heme Oxygenase-1 / metabolism
  • In Situ Nick-End Labeling
  • Iron / metabolism
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Siderophores / therapeutic use*
  • Subarachnoid Hemorrhage / complications*
  • Subarachnoid Hemorrhage / mortality

Substances

  • Siderophores
  • Iron
  • Heme Oxygenase-1
  • Deferoxamine