Role of Nrf2 in protection against intracerebral hemorrhage injury in mice.

Abstract

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.

• Authors: Jian Wang, Jocelyn Fields, Chunying Zhao, John Langer, Rajesh K Thimmulappa, Thomas W Kensler, Masayuki Yamamoto, Shyam Biswal, Sylvain Doré
• Journal: Free radical biology & medicine (Free Radic Biol Med) Vol. 43 Issue 3 Pg. 408-14 (Aug 01 2007) ISSN: 0891-5849 [Print] United States
• PMID: 17602956 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

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

Topics

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