Iron-induced necrotic brain cell death in rats with different aerobic capacity

Transl Stroke Res. 2015 Jun;6(3):215-23. doi: 10.1007/s12975-015-0388-8. Epub 2015 Feb 5.

Abstract

Brain iron overload has a key role in brain injury after intracerebral hemorrhage (ICH). Our recent study demonstrated that ICH-induced brain injury was greater in low capacity runner (LCR) than in high capacity runner (HCR) rats. The present study examines whether iron-induced brain injury differs between LCRs and HCRs. Adult male LCR and HCR rats had an intracaudate injection of iron or saline. Rats were euthanized at 2 and at 24 h after T2 magnetic resonance imaging, and the brains were used for immunostaining and Western blotting. LCRs had more hemispheric swelling, T2 lesion volumes, blood-brain barrier disruption, and neuronal death at 24 h after iron injection (p < 0.05). Many propidium iodide (PI)-positive cells, indicative of necrotic cell death, were observed in the ipsilateral basal ganglia of both HCRs and LCRs at 2 h after iron injection. PI fluorescence intensity was higher in LCRs than in HCRs. In addition, membrane attack complex (MAC) expression was increased at 2 h after iron injection and was higher in LCRs than in HCRs. The PI-positive cells co-localized with MAC-positive cells in the ipsilateral basal ganglia. Iron induces more severe necrotic brain cell death, brain swelling, and blood-brain barrier disruption in LCR rats, which may be related with complement activation and MAC formation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / pathology
  • Caudate Nucleus / drug effects
  • Caudate Nucleus / metabolism
  • Caudate Nucleus / pathology*
  • Cell Death / drug effects
  • Complement Membrane Attack Complex / metabolism
  • Iron / toxicity*
  • Male
  • Necrosis
  • Neurons / drug effects
  • Neurons / metabolism
  • Neurons / pathology*
  • Physical Conditioning, Animal*
  • Rats

Substances

  • Complement Membrane Attack Complex
  • Iron