Minocycline Effects on Intracerebral Hemorrhage-Induced Iron Overload in Aged Rats: Brain Iron Quantification With Magnetic Resonance Imaging

Stroke. 2018 Apr;49(4):995-1002. doi: 10.1161/STROKEAHA.117.019860. Epub 2018 Mar 6.


Background and purpose: Brain iron overload is a key factor causing brain injury after intracerebral hemorrhage (ICH). This study quantified brain iron levels after ICH with magnetic resonance imaging R2* mapping. The effect of minocycline on iron overload and ICH-induced brain injury in aged rats was also determined.

Methods: Aged (18 months old) male Fischer 344 rats had an intracerebral injection of autologous blood or saline, and brain iron levels were measured by magnetic resonance imaging R2* mapping. Some ICH rats were treated with minocycline or vehicle. The rats were euthanized at days 7 and 28 after ICH, and brains were used for immunohistochemistry and Western blot analyses. Magnetic resonance imaging (T2-weighted, T2* gradient-echo, and R2* mapping) sequences were performed at different time points.

Results: ICH-induced brain iron overload in the perihematomal area could be quantified by R2* mapping. Minocycline treatment reduced brain iron accumulation, T2* lesion volume, iron-handling protein upregulation, neuronal cell death, and neurological deficits (P<0.05).

Conclusions: Magnetic resonance imaging R2* mapping is a reliable and noninvasive method, which can quantitatively measure brain iron levels after ICH. Minocycline reduced ICH-related perihematomal iron accumulation and brain injury in aged rats.

Keywords: cerebral hemorrhage; iron; magnetic resonance imaging; minocycline; upregulation.

Publication types

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

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Blotting, Western
  • Brain / diagnostic imaging
  • Brain / drug effects*
  • Brain / metabolism
  • Brain / pathology
  • Cell Death / drug effects*
  • Cerebral Hemorrhage / complications
  • Cerebral Hemorrhage / diagnostic imaging*
  • Disease Models, Animal
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / drug effects
  • Dopamine and cAMP-Regulated Phosphoprotein 32 / metabolism
  • Ferritins / drug effects
  • Ferritins / metabolism
  • Heme Oxygenase (Decyclizing) / drug effects
  • Heme Oxygenase (Decyclizing) / metabolism
  • Immunohistochemistry
  • Iron Overload / diagnostic imaging*
  • Iron Overload / etiology
  • Magnetic Resonance Imaging
  • Male
  • Minocycline / pharmacology*
  • Neurons / drug effects*
  • Neurons / pathology
  • Rats
  • Rats, Inbred F344


  • Anti-Bacterial Agents
  • Dopamine and cAMP-Regulated Phosphoprotein 32
  • Ppp1r1b protein, rat
  • Ferritins
  • Heme Oxygenase (Decyclizing)
  • Hmox1 protein, rat
  • Minocycline