PMID- 23717624
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20211021
IS  - 1932-6203 (Electronic)
IS  - 1932-6203 (Linking)
VI  - 8
IP  - 5
DP  - 2013
TI  - The prevalence and phenotype of activated microglia/macrophages within the spinal 
      cord of the hyperostotic mouse (twy/twy) changes in response to chronic 
      progressive spinal cord compression: implications for human cervical compressive 
      myelopathy.
PG  - e64528
LID - 10.1371/journal.pone.0064528 [doi]
LID - e64528
AB  - BACKGROUND: Cervical compressive myelopathy, e.g. due to spondylosis or 
      ossification of the posterior longitudinal ligament is a common cause of spinal 
      cord dysfunction. Although human pathological studies have reported neuronal loss 
      and demyelination in the chronically compressed spinal cord, little is known 
      about the mechanisms involved. In particular, the neuroinflammatory processes 
      that are thought to underlie the condition are poorly understood. The present 
      study assessed the localized prevalence of activated M1 and M2 
      microglia/macrophages in twy/twy mice that develop spontaneous cervical spinal 
      cord compression, as a model of human disease. METHODS: Inflammatory cells and 
      cytokines were assessed in compressed lesions of the spinal cords in 12-, 18- and 
      24-weeks old twy/twy mice by immunohistochemical, immunoblot and flow cytometric 
      analysis. Computed tomography and standard histology confirmed a progressive 
      spinal cord compression through the spontaneously development of an impinging 
      calcified mass. RESULTS: The prevalence of CD11b-positive cells, in the 
      compressed spinal cord increased over time with a concurrent decrease in neurons. 
      The CD11b-positive cell population was initially formed of arginase-1- and 
      CD206-positive M2 microglia/macrophages, which later shifted towards iNOS- and 
      CD16/32-positive M1 microglia/macrophages. There was a transient increase in 
      levels of T helper 2 (Th2) cytokines at 18 weeks, whereas levels of Th1 cytokines 
      as well as brain-derived neurotrophic factor (BDNF), nerve growth factor (NGF) 
      and macrophage antigen (Mac)-2 progressively increased. CONCLUSIONS: Spinal cord 
      compression was associated with a temporal M2 microglia/macrophage response, 
      which may act as a possible repair or neuroprotective mechanism. However, the 
      persistence of the neural insult also associated with persistent expression of 
      Th1 cytokines and increased prevalence of activated M1 microglia/macrophages, 
      which may lead to neuronal loss and demyelination despite the presence of 
      neurotrophic factors. This understanding of the aetiopathology of chronic spinal 
      cord compression is of importance in the development of new treatment targets in 
      human disease.
FAU - Hirai, Takayuki
AU  - Hirai T
AD  - Department of Orthopaedics and Rehabilitation Medicine, Faculty of Medical 
      Sciences, University of Fukui, Eiheiji, Fukui, Japan.
FAU - Uchida, Kenzo
AU  - Uchida K
FAU - Nakajima, Hideaki
AU  - Nakajima H
FAU - Guerrero, Alexander Rodriguez
AU  - Guerrero AR
FAU - Takeura, Naoto
AU  - Takeura N
FAU - Watanabe, Shuji
AU  - Watanabe S
FAU - Sugita, Daisuke
AU  - Sugita D
FAU - Yoshida, Ai
AU  - Yoshida A
FAU - Johnson, William E B
AU  - Johnson WE
FAU - Baba, Hisatoshi
AU  - Baba H
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130524
PL  - United States
TA  - PLoS One
JT  - PloS one
JID - 101285081
RN  - 0 (Cytokines)
RN  - 0 (Nerve Growth Factors)
SB  - IM
MH  - Animals
MH  - Cytokines/metabolism
MH  - Disease Models, Animal
MH  - Humans
MH  - Hyperostosis/*complications/diagnosis
MH  - *Macrophage Activation
MH  - Macrophages/*immunology/metabolism
MH  - Mice
MH  - Microglia/*immunology/metabolism
MH  - Nerve Growth Factors/metabolism
MH  - Neurons/metabolism/pathology
MH  - Phagocytosis/immunology
MH  - *Phenotype
MH  - Prevalence
MH  - Spinal Cord/immunology/metabolism/pathology
MH  - Spinal Cord Compression/diagnosis/*etiology
MH  - T-Lymphocytes, Helper-Inducer/immunology/metabolism
MH  - Th2 Cells
MH  - Tomography, X-Ray Computed
PMC - PMC3663759
COIS- Competing Interests: The authors have declared that no competing interests exist.
EDAT- 2013/05/30 06:00
MHDA- 2013/12/16 06:00
PMCR- 2013/05/24
CRDT- 2013/05/30 06:00
PHST- 2013/01/12 00:00 [received]
PHST- 2013/04/16 00:00 [accepted]
PHST- 2013/05/30 06:00 [entrez]
PHST- 2013/05/30 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
PHST- 2013/05/24 00:00 [pmc-release]
AID - PONE-D-13-02138 [pii]
AID - 10.1371/journal.pone.0064528 [doi]
PST - epublish
SO  - PLoS One. 2013 May 24;8(5):e64528. doi: 10.1371/journal.pone.0064528. Print 2013.