Role of Nrf2 in protection against intracerebral hemorrhage injury in mice.
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.
Wang
Jian
J
Anesthesiology/Critical Care Medicine, Johns Hopkins University, School of Medicine, Baltimore, MD 21205, USA.
Fields
Jocelyn
J
Zhao
Chunying
C
Langer
John
J
Thimmulappa
Rajesh K
RK
Kensler
Thomas W
TW
Yamamoto
Masayuki
M
Biswal
Shyam
S
Doré
Sylvain
S
D000818:Animals; D002543:Cerebral Hemorrhage / Q000473:pathology / Q000517:prevention & control*; D045304:Cytochromes c / Q000378:metabolism; D004249:DNA Damage / Q000502:physiology; D007962:Leukocytes / Q000502:physiology; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000172:deficiency / Q000502:physiology*; D017382:Reactive Oxygen Species / Q000378:metabolism
D051267:NF-E2-Related Factor 2; C495636:Nfe2l2 protein, mouse; D017382:Reactive Oxygen Species; D045304:Cytochromes c