BACKGROUND 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 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.
BACKGROUND 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 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-deficientmice 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.
Authors: Crissey L Pascale; Alejandra N Martinez; Christopher Carr; David M Sawyer; Marcelo Ribeiro-Alves; Mimi Chen; Devon B O'Donnell; Jessie J Guidry; Peter S Amenta; Aaron S Dumont Journal: J Cereb Blood Flow Metab Date: 2019-06-20 Impact factor: 6.200
Authors: Jeffrey A Johnson; Delinda A Johnson; Andrew D Kraft; Marcus J Calkins; Rebekah J Jakel; Marcelo R Vargas; Pei-Chun Chen Journal: Ann N Y Acad Sci Date: 2008-12 Impact factor: 5.691