Effectiveness of deferoxamine on ferric chloride-induced epilepsy in rats

Brain Res. 2017 Mar 1:1658:25-30. doi: 10.1016/j.brainres.2017.01.001. Epub 2017 Jan 4.

Abstract

Iron overload has been regarded as a common cause for refractory epilepsies in patients after hemorrhagic strokes. This study is to examine the potential epilepsy control effect of deferoxamine (DFO), an iron chelator, on a ferric chloride-induced epilepsy rat model. Twenty four rats were divided into 4 groups: group I is blank control group, group II is sham group with intracortical injection of saline, group III is epilepsy group with intracortical injection of iron and saline treatment, group IV is treatment group with intracortical injection of iron and DFO treatment. For the DFO intervention group, a daily dose of 100mg/kg DFO via peritoneal injection was applied for 14days. Outcomes were evaluated by behavioral study, electroencephalography (EEG), magnetic resonance imaging (MRI) scan and tissue analysis. Epilepsies according to behavioral observations and EEG analysis were significantly suppressed after intervention of DFO. Reduction of iron content in the brain cortex was proved by diminished low signal area on T2-MRI images (p=0.006) and tissue analysis (p<0.001), simultaneously the superoxide dismutase (SOD) activity increased (p<0.001). Western blot analysis demonstrated the decreasing of local transferrin after DFO treatment. DFO is efficient at Fe clearance, thus helpful in epilepsy control. This finding implies potential therapeutic value of DFO in patients with refractory epilepsy after hemorrhagic stroke.

Keywords: Deferoxamine; Electroencephalography; Epilepsy; Iron; MRI; Rats.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Anticonvulsants / pharmacology*
  • Blotting, Western
  • Brain / diagnostic imaging
  • Brain / drug effects
  • Brain / pathology
  • Brain / physiopathology
  • Chlorides
  • Deferoxamine / pharmacology*
  • Disease Models, Animal
  • Drug Evaluation, Preclinical
  • Electroencephalography
  • Epilepsy / diagnostic imaging
  • Epilepsy / drug therapy*
  • Epilepsy / pathology
  • Epilepsy / physiopathology
  • Ferric Compounds
  • Ferritins / metabolism
  • Iron / metabolism
  • Magnetic Resonance Imaging
  • Male
  • Random Allocation
  • Rats, Sprague-Dawley
  • Siderophores / pharmacology*
  • Superoxide Dismutase / metabolism
  • Transferrin / metabolism

Substances

  • Anticonvulsants
  • Chlorides
  • Ferric Compounds
  • Siderophores
  • Transferrin
  • Ferritins
  • Iron
  • Superoxide Dismutase
  • Deferoxamine
  • ferric chloride