Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance.
Cleaning up after ICH: the role of Nrf2 in modulating microglia function and hematoma clearance.
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DOI：
10.1111/jnc.12974
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发表时间：
2015-04
影响因子：
4.7
通讯作者：
Aronowski J
中科院分区：
文献类型：
--
作者：
Zhao X;Sun G;Ting SM;Song S;Zhang J;Edwards NJ;Aronowski J
As a consequence of intracerebral hemorrhage (ICH), blood components enter brain parenchyma causing progressive damage to the surrounding brain. Unless hematoma is cleared, the reservoirs of blood continue to inflict injury to neurovascular structures and blunt the brain repair processes. Microglia/macrophages (MM Φ) represent the primary phagocytic system that mediates the cleanup of hematoma. Thus the efficacy of phagocytic function by MM Φ is an essential step in limiting ICH-mediated damage. By using primary microglia to model red blood cell (main component of hematoma) clearance, we studied the role of transcription factor Nrf2, a master-regulator of anti-oxidative defense, in the hematoma clearance process. We showed that in cultured microglia, activators of Nrf2 1) induce anti-oxidative defense components, 2) reduce peroxide formation, 3) upregulate phagocytosis-mediating scavenger receptor CD36, and 4) enhance RBC phagocytosis. Through inhibiting Nrf2 or CD36 in microglia, by DNA-decoy or neutralizing antibody, we documented the important role of Nrf2 and CD36 in RBC phagocytosis. Using autologous blood injection ICH model to measure hematoma resolution, we showed that Nrf2 activator, sulforaphane, injected to animals after the onset of ICH, induced CD36 expression in ICH-affected brain and improved hematoma clearance in rats and wild-type mice, but expectedly not in Nrf2-knockout-(KO) mice. Normal hematoma clearance was impaired in Nrf2-KO mice. Our experiments suggest that Nrf2 in microglia play an important role in augmenting the anti-oxidative capacity, phagocytosis and hematoma clearance after ICH.
