Brain Edema XIII pp 194-198

Iron-induced oxidative brain injury after experimental intracerebral hemorrhage

  • T. Nakamura
  • R. F. Keep
  • Y. Hua
  • S. Nagao
  • J. T. Hoff
  • G. Xi
Part of the Acta Neurochirurgica Supplementum book series (NEUROCHIRURGICA, volume 96)

Summary

We investigated the occurrence of DNA damage in brain after intracerebral hemorrhage (ICH) and the role of iron in such injury.

Male Sprague-Dawley rats received an infusion of 100 µL autologous whole blood or 30 µL FeCl2 into the right basal ganglia and were sacrificed 1, 3, or 7 days later. 8-hydroxyl-2′-deoxyguanosine (8-OHdG) was analyzed by immunohistochemistry, while the number of apurinic/apyrimidinic abasic sites (AP sites) was also quantified. 8-OHdG and AP sites are two hallmarks of DNA oxidation. DNA damage was also examined using PANT and TUNEL labeling. Dinitrophenyl (DNP) was measured by Western blot to compare the time course of protein oxidative damage to that of DNA. DNA repair APE/Ref-1 and Ku-proteins were also measured by Western blot. Bipyridine, a ferrous iron chelator, was used to examine the role of iron in ICH-induced oxidative brain injury.

An increase in 8-OHdG, AP sites, and DNP levels, and a decrease in APE/Ref-1 and Ku levels were observed. Abundant PANT-positive cells were also observed in the perihematomal area 3 days after ICH. Bipyridine attenuated ICH-induced changes in PANT and DNP. These results suggest that iron-induced oxidation causes DNA damage in brain after ICH and that iron is a therapeutic target for ICH.

Keywords

Intracerebral hemorrhage iron oxidative DNA injury 8-OHdG AP sites DNP PANT APE/Ref-1 Ku-proteins brain edema 

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Copyright information

© Springer-Verlag 2006

Authors and Affiliations

  • T. Nakamura
    • 1
    • 2
  • R. F. Keep
    • 1
  • Y. Hua
    • 1
  • S. Nagao
    • 2
  • J. T. Hoff
    • 1
  • G. Xi
    • 1
  1. 1.Department of NeurosurgeryUniversity of MichiganAnn ArborUSA
  2. 2.Department of Neurological SurgeryKagawa University Faculty of MedicineKagawaJapan

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