TY - JOUR
T1 - Role of Nrf2 in protection against intracerebral hemorrhage injury in mice
AU - Wang, Jian
AU - Fields, Jocelyn
AU - Zhao, Chunying
AU - Langer, John
AU - Thimmulappa, Rajesh K.
AU - Kensler, Thomas W.
AU - Yamamoto, Masayuki
AU - Biswal, Shyam
AU - Doré, Sylvain
N1 - Funding Information:
This work was supported by an American Heart Association SDG 0630223N (J.W.); NIH Grants HL081205 and P30ES0389 (SB); and AT001836, AA014911, AT002113, and NS046400 (S.D.). We thank Claire Levine for assistance with the manuscript and all members of the Doré lab for their insightful comments.
PY - 2007/8/1
Y1 - 2007/8/1
N2 - 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.
AB - 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.
KW - DNA damage
KW - Free radicals
KW - Inflammation
KW - NF-E2-related factor 2
KW - Reactive oxygen species
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U2 - 10.1016/j.freeradbiomed.2007.04.020
DO - 10.1016/j.freeradbiomed.2007.04.020
M3 - Article
C2 - 17602956
AN - SCOPUS:34250854714
SN - 0891-5849
VL - 43
SP - 408
EP - 414
JO - Free Radical Biology and Medicine
JF - Free Radical Biology and Medicine
IS - 3
ER -