PMID- 23404620
OWN - NLM
STAT- MEDLINE
DCOM- 20131216
LR  - 20240322
IS  - 1098-1136 (Electronic)
IS  - 0894-1491 (Print)
IS  - 0894-1491 (Linking)
VI  - 61
IP  - 5
DP  - 2013 May
TI  - Microglia and macrophages differentially modulate cell death after brain injury 
      caused by oxygen-glucose deprivation in organotypic brain slices.
PG  - 813-24
LID - 10.1002/glia.22478 [doi]
AB  - Macrophage can adopt several phenotypes, process call polarization, which is 
      crucial for shaping inflammatory responses to injury. It is not known if 
      microglia, a resident brain macrophage population, polarizes in a similar way, 
      and whether specific microglial phenotypes modulate cell death in response to 
      brain injury. In this study, we show that both BV2-microglia and mouse bone 
      marrow derived macrophages (BMDMs) were able to adopt different phenotypes after 
      LPS (M1) or IL-4 (M2) treatment in vitro, but regulated cell death differently 
      when added to mouse organotypic hippocampal brain slices. BMDMs induced cell 
      death when added to control slices and exacerbated damage when combined with 
      oxygen-glucose deprivation (OGD), independently of their phenotype. In contrast, 
      vehicle- and M2-BV2-microglia were protective against OGD-induced death. Direct 
      treatment of brain slices with IL-4 (without cell addition) was protective 
      against OGD and induced an M2 phenotype in the slice. In vivo, intracerebral 
      injection of LPS or IL-4 in mice induced microglial phenotypes similar to the 
      phenotypes observed in brain slices and in cultured cells. After injury induced 
      by middle cerebral artery occlusion, microglial cells did not adopt classical 
      M1/M2 phenotypes, suggesting that another subtype of regulatory phenotype was 
      induced. This study highlights functional differences between macrophages and 
      microglia, in response to brain injury with fundamentally different outcomes, 
      even if both populations were able to adopt M1 or M2 phenotypes. These data 
      suggest that macrophages infiltrating the brain from the periphery after an 
      injury may be cytotoxic, independently of their phenotype, while microglia may be 
      protective.
CI  - Copyright (c) 2013 Wiley Periodicals, Inc.
FAU - Girard, Sylvie
AU  - Girard S
AD  - Faculty of Life Sciences, University of Manchester, Manchester, United Kingdom. 
      sylvie.girard@manchester.ac.uk
FAU - Brough, David
AU  - Brough D
FAU - Lopez-Castejon, Gloria
AU  - Lopez-Castejon G
FAU - Giles, James
AU  - Giles J
FAU - Rothwell, Nancy J
AU  - Rothwell NJ
FAU - Allan, Stuart M
AU  - Allan SM
LA  - eng
GR  - FS/10/73/28464/BHF_/British Heart Foundation/United Kingdom
GR  - G0802001/MRC_/Medical Research Council/United Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
GR  - CAPMC/CIHR/Canada
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130213
PL  - United States
TA  - Glia
JT  - Glia
JID - 8806785
RN  - IY9XDZ35W2 (Glucose)
SB  - IM
MH  - Animals
MH  - Brain Injuries/*metabolism/*pathology
MH  - Cell Death/physiology
MH  - Cell Hypoxia/physiology
MH  - Cells, Cultured
MH  - Glucose/*deficiency
MH  - Hippocampus/metabolism/*pathology
MH  - Macrophages/*metabolism/*pathology
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Microglia/*metabolism/*pathology
MH  - Organ Culture Techniques
MH  - Organ Specificity/physiology
PMC - PMC3644876
EDAT- 2013/02/14 06:00
MHDA- 2013/12/18 06:00
CRDT- 2013/02/14 06:00
PHST- 2010/08/31 00:00 [received]
PHST- 2013/01/10 00:00 [accepted]
PHST- 2013/02/14 06:00 [entrez]
PHST- 2013/02/14 06:00 [pubmed]
PHST- 2013/12/18 06:00 [medline]
AID - 10.1002/glia.22478 [doi]
PST - ppublish
SO  - Glia. 2013 May;61(5):813-24. doi: 10.1002/glia.22478. Epub 2013 Feb 13.