Transcription factor Nrf2 protects the brain from damage produced by intracerebral hemorrhage.
OBJECTIVE
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 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.
Zhao
Xiurong
X
Department of Neurology, University of Texas at Health Science Center at Houston, Houston, TX 77030, USA.
Sun
Guanghua
G
Zhang
Jie
J
Strong
Roger
R
Dash
Pramod K
PK
Kan
Yuet Wai
YW
Grotta
James C
JC
Aronowski
Jaroslaw
J
D021581:Active Transport, Cell Nucleus; D000818:Animals; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D002467:Cell Nucleus / Q000378:metabolism; D002543:Cerebral Hemorrhage / Q000235:genetics* / Q000378:metabolism*; D017931:DNA Primers / Q000737:chemistry; D017879:Isothiocyanates; D051379:Mice; D008810:Mice, Inbred C57BL; D051267:NF-E2-Related Factor 2 / Q000378:metabolism / Q000502:physiology*; D018696:Neuroprotective Agents / Q000494:pharmacology; D009504:Neutrophils / Q000378:metabolism; D018384:Oxidative Stress; D010477:Perfusion; D009195:Peroxidase / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D013454:Sulfoxides; D013861:Thiocyanates / Q000494:pharmacology
D017931:DNA Primers; D017879:Isothiocyanates; D051267:NF-E2-Related Factor 2; D018696:Neuroprotective Agents; D013454:Sulfoxides; D013861:Thiocyanates; D009195:Peroxidase; C016766:sulforaphane