PMID- 29358565
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1674-8301 (Print)
IS  - 2352-4685 (Electronic)
IS  - 1674-8301 (Linking)
VI  - 32
IP  - 2
DP  - 2018 Mar 26
TI  - Microglia activation mediated by toll-like receptor-4 impairs brain white matter 
      tracts in rats.
PG  - 136-144
LID - 10.7555/JBR.32.20170033 [doi]
AB  - Microglia activation and white matter injury coexist after repeated episodes of 
      mild brain trauma and ischemic stroke. Axon degeneration and demyelination can 
      activate microglia; however, it is unclear whether early microglia activation can 
      impair the function of white matter tracts and lead to injury. Rat corpus 
      callosum (CC) slices were treated with lipopolysaccharide (LPS) or LPS + 
      Rhodobacter sphaeroides (RS)-LPS that is a toll-like receptor 4 (TLR-4) 
      antagonist. Functional changes reflected by the change of axon compound action 
      potentials (CAPs) and the accumulation of beta-amyloid precursor protein (beta-APP) in 
      CC nerve fibers. Microglia activation was monitored by ionized calcium binding 
      adaptor-1 immunofluorescent stain, based on well-established morphological 
      criteria and paralleled proportional area measurement. Input-output (I/O) curves 
      of CAPs in response to increased stimuli were significantly downshifted in a 
      dose-dependent manner in LPS (0.2, 0.5 and 1.0 microg/mL)-treated slices, implying 
      that axons neurophysiological function was undermined. LPS caused 
      significant beta-APP accumulation in CC tissues, reflecting the 
      deterioration of fast axon transport. LPS-induced I/O curve downshift and beta-APP 
      accumulation were significantly reversed by the pre-treatment or 
      co-incubation with RS-LPS. RS-LPS alone did not change the I/O curve. The degree 
      of malfunction was correlated with microglia activation, as was shown by the 
      measurements of proportional areas. Function of CC nerve fibers was evidently 
      impaired by microglia activation and reversed by a TLP-4 antagonist, suggesting 
      that the TLP-4 pathway lead to microglia activation.
FAU - Yang, Xinglong
AU  - Yang X
AD  - Department of Neurosurgery, Affiliated Hospital to Academy of Military Medicine 
      Sciences, Beijing 100071, China.
FAU - Zhang, Jing-Dong
AU  - Zhang JD
AD  - Department of Pharmacology & Experimental Neurosciences, University of Nebraska 
      Medical Center, Omaha, NE 68198, USA.
FAU - Duan, Lian
AU  - Duan L
AD  - Department of Neurosurgery, Affiliated Hospital to Academy of Military Medicine 
      Sciences, Beijing 100071, China.
FAU - Xiong, Huan-Gui
AU  - Xiong HG
AD  - Department of Pharmacology & Experimental Neurosciences, University of Nebraska 
      Medical Center, Omaha, NE 68198, USA.
FAU - Jiang, Yan-Ping
AU  - Jiang YP
AD  - Department of Otolaryngology, the 306th PLA Hospital, Beijing 100101, China.
FAU - Liang, Hou-Cheng
AU  - Liang HC
AD  - Xi'an Bright Eye Hospital, Xi'an, Shaanxi 710000, China.
LA  - eng
GR  - R01 NS077873/NS/NINDS NIH HHS/United States
PT  - Journal Article
PL  - China
TA  - J Biomed Res
JT  - Journal of biomedical research
JID - 101551157
PMC - PMC5895568
COIS- The authors reported no conflict of interests.
EDAT- 2018/01/24 06:00
MHDA- 2018/01/24 06:01
PMCR- 2018/03/26
CRDT- 2018/01/24 06:00
PHST- 2018/01/24 06:00 [pubmed]
PHST- 2018/01/24 06:01 [medline]
PHST- 2018/01/24 06:00 [entrez]
PHST- 2018/03/26 00:00 [pmc-release]
AID - 10.7555/JBR.32.20170033 [doi]
PST - ppublish
SO  - J Biomed Res. 2018 Mar 26;32(2):136-144. doi: 10.7555/JBR.32.20170033.