PMID- 25328080
OWN - NLM
STAT- MEDLINE
DCOM- 20150527
LR  - 20220321
IS  - 1471-4159 (Electronic)
IS  - 0022-3042 (Print)
IS  - 0022-3042 (Linking)
VI  - 133
IP  - 1
DP  - 2015 Apr
TI  - Cleaning up after ICH: the role of Nrf2 in modulating microglia function and 
      hematoma clearance.
PG  - 144-52
LID - 10.1111/jnc.12974 [doi]
AB  - 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 (MMPhi) 
      represent the primary phagocytic system that mediates the cleanup of hematoma. 
      Thus, the efficacy of phagocytic function by MMPhi is an essential step in limiting 
      ICH-mediated damage. Using primary microglia to model red blood cell (main 
      component of hematoma) clearance, we studied the role of transcription factor 
      nuclear factor-erythroid 2 p45-related factor 2 (Nrf2), a master-regulator of 
      antioxidative defense, in the hematoma clearance process. We showed that in 
      cultured microglia, activators of Nrf2 (i) induce antioxidative defense 
      components, (ii) reduce peroxide formation, (iii) up-regulate 
      phagocytosis-mediating scavenger receptor CD36, and (iv) enhance red blood cells 
      (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 antioxidative capacity, phagocytosis, and hematoma clearance after 
      ICH.
CI  - (c) 2014 International Society for Neurochemistry.
FAU - Zhao, Xiurong
AU  - Zhao X
AD  - Stroke Program - Department of Neurology, University of Texas Health Science 
      Center, Medical School at Houston, Houston, Texas, USA.
FAU - Sun, Guanghua
AU  - Sun G
FAU - Ting, Shun-Ming
AU  - Ting SM
FAU - Song, Shen
AU  - Song S
FAU - Zhang, Jie
AU  - Zhang J
FAU - Edwards, Nancy J
AU  - Edwards NJ
FAU - Aronowski, Jaroslaw
AU  - Aronowski J
LA  - eng
GR  - R01 NS060768/NS/NINDS NIH HHS/United States
GR  - R01 NS064109/NS/NINDS NIH HHS/United States
GR  - R01NS060768/NS/NINDS NIH HHS/United States
GR  - R01NS064109/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20141124
PL  - England
TA  - J Neurochem
JT  - Journal of neurochemistry
JID - 2985190R
RN  - 0 (CD36 Antigens)
RN  - 0 (Hydroquinones)
RN  - 0 (Isothiocyanates)
RN  - 0 (NF-E2 Transcription Factor, p45 Subunit)
RN  - 0 (Sulfoxides)
RN  - BBX060AN9V (Hydrogen Peroxide)
RN  - C12674942B (2-tert-butylhydroquinone)
RN  - GA49J4310U (sulforaphane)
SB  - IM
MH  - Animals
MH  - Brain/pathology
MH  - CD36 Antigens/biosynthesis
MH  - Cell Count
MH  - Cells, Cultured
MH  - Cerebral Hemorrhage/*metabolism/pathology
MH  - Hydrogen Peroxide/metabolism
MH  - Hydroquinones/pharmacology
MH  - Isothiocyanates/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Microglia/*metabolism
MH  - NF-E2 Transcription Factor, p45 Subunit/genetics/*metabolism
MH  - Phagocytosis/drug effects
MH  - Sulfoxides
PMC - PMC4361377
MID - NIHMS638161
OTO - NOTNLM
OT  - Nrf2
OT  - hematoma
OT  - intracerebral hemorrhage
OT  - microglia
OT  - phagocytosis
OT  - sulforaphane
COIS- The authors have no conflicts of interest to declare.
EDAT- 2014/10/21 06:00
MHDA- 2015/05/28 06:00
PMCR- 2016/04/01
CRDT- 2014/10/21 06:00
PHST- 2014/08/21 00:00 [received]
PHST- 2014/10/07 00:00 [revised]
PHST- 2014/10/13 00:00 [accepted]
PHST- 2014/10/21 06:00 [entrez]
PHST- 2014/10/21 06:00 [pubmed]
PHST- 2015/05/28 06:00 [medline]
PHST- 2016/04/01 00:00 [pmc-release]
AID - 10.1111/jnc.12974 [doi]
PST - ppublish
SO  - J Neurochem. 2015 Apr;133(1):144-52. doi: 10.1111/jnc.12974. Epub 2014 Nov 24.