Role of Nrf2 in protection against intracerebral hemorrhage injury in mice

Free Radic Biol Med. 2007 Aug 1;43(3):408-14. doi: 10.1016/j.freeradbiomed.2007.04.020. Epub 2007 Apr 29.


Nrf2 is a key transcriptional factor for antioxidant response element (ARE)-regulated genes. While its beneficial role has been described for stroke, its contribution to intracerebral hemorrhage (ICH)-induced early brain injury remains to be determined. Using wild-type (WT) and Nrf2 knockout (Nrf2(-/-)) mice, the role of Nrf2 in ICH induced by intracerebral injection of collagenase was investigated. The results showed that injury volume was significantly larger in Nrf2(-/-) mice than in WT controls 24 h after induction of ICH (P<0.05), an outcome that correlated with neurological deficits. This exacerbation of brain injury in Nrf2(-/-) mice was also associated with an increase in leukocyte infiltration, production of reactive oxygen species, DNA damage, and cytochrome c release during the critical early phase of the post-ICH period. In combination, these results suggest that Nrf2 reduces ICH-induced early brain injury, possibly by providing protection against leukocyte-mediated free radical oxidative damage.

Publication types

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

MeSH terms

  • Animals
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / prevention & control*
  • Cytochromes c / metabolism
  • DNA Damage / physiology
  • Leukocytes / physiology
  • Mice
  • NF-E2-Related Factor 2 / deficiency
  • NF-E2-Related Factor 2 / physiology*
  • Reactive Oxygen Species / metabolism


  • NF-E2-Related Factor 2
  • Nfe2l2 protein, mouse
  • Reactive Oxygen Species
  • Cytochromes c