Effects of deferoxamine on blood-brain barrier disruption after subarachnoid hemorrhage

PLoS One. 2017 Mar 1;12(3):e0172784. doi: 10.1371/journal.pone.0172784. eCollection 2017.

Abstract

Blood brain barrier (BBB) disruption is a key mechanism of subarachnoid hemorrhage (SAH)-induced brain injury. This study examined the mechanism of iron-induced BBB disruption after SAH and investigated the potential therapeutic effect of iron chelation on SAH. Male adult Sprague-Dawley rats had an endovascular perforation of left internal carotid artery bifurcation or sham operation. The rats were treated with deferoxamine (DFX) or vehicle (100mg/kg) for a maximum of 7 days. Brain edema, BBB leakage, behavioral and cognitive impairment were examined. In SAH rat, the peak time of brain edema and BBB impairment in the cortex was at day 3 after SAH. SAH resulted in a significant increase in ferritin expression in the cortex. The ferritin positive cells were colocalized with endothelial cells, pericytes, astrocytes, microglia and neurons. Compared with vehicle, DFX caused less ferritin upregulation, brain water content, BBB impairment, behavioral and cognitive deficits in SAH rats. The results suggest iron overload could be a therapeutic target for SAH induced BBB damage.

MeSH terms

  • Animals
  • Behavior, Animal / drug effects
  • Blood-Brain Barrier* / metabolism
  • Blood-Brain Barrier* / pathology
  • Blood-Brain Barrier* / physiopathology
  • Brain Edema / drug therapy
  • Brain Edema / metabolism
  • Brain Edema / pathology
  • Brain Edema / physiopathology
  • Brain Injuries / drug therapy
  • Brain Injuries / metabolism
  • Brain Injuries / pathology
  • Brain Injuries / physiopathology
  • Cognition / drug effects
  • Deferoxamine / pharmacology*
  • Iron Overload / metabolism
  • Iron Overload / pathology
  • Iron Overload / physiopathology
  • Male
  • Rats
  • Rats, Sprague-Dawley
  • Subarachnoid Hemorrhage* / drug therapy
  • Subarachnoid Hemorrhage* / metabolism
  • Subarachnoid Hemorrhage* / pathology
  • Subarachnoid Hemorrhage* / physiopathology

Substances

  • Deferoxamine

Grants and funding

This study was supported by grants 81500987 from the National Natural Science Foundation of China (NSFC) and grants 15140902300 from Science and Technology Commission of Shanghai Municipality(STCSM), http://www.nsfc.gov.cn.