Transcription Factor Nrf2 Protects the Brain From Damage Produced by Intracerebral Hemorrhage

X. Zhao, G. Sun, J. Zhang, R. Strong, P. K. Dash, Y. W. Kan, J. C. Grotta, J. Aronowski
2007 Stroke  
and Purpose-Intracerebral hemorrhage (ICH) remains a major medical problem for which there is no effective treatment. Oxidative and cytotoxic damage plays an important role in ICH pathogenesis and may represent a target for treatment of ICH. Recent studies have suggested that nuclear factor-erythroid 2-related factor 2 (Nrf2), a pleiotropic transcription factor, may play a key role in protecting cells from cytotoxic/oxidative damage. This study evaluated the role of Nrf2 in protecting the brain
more » ... from ICH-mediated damage. Methods-Sprague-Dawley rats and Nrf2-deficient or control mice received intracerebral injection of autologous blood to mimic ICH. Sulforaphane was used to activate Nrf2. Oxidative stress, the presence of myeloperoxidase-positive cells (neutrophils) in ICH-affected brains, and behavioral dysfunction were assessed to determine the extent of ICH-mediated damage. Results-Sulforaphane activated Nrf2 in ICH-affected brain tissue and reduced neutrophil count, oxidative damage, and behavioral deficits caused by ICH. Nrf2-deficient mice demonstrated more severe neurologic deficits after ICH and did not benefit from the protective effect of sulforaphane. Conclusions-Nrf2 may represent a strategic target for ICH therapies. (Stroke. 2007;38:3280-3286.)
doi:10.1161/strokeaha.107.486506 pmid:17962605 fatcat:tb6aav23rnahnbcf3c3z5jsrhq