PMID- 30386214
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20201001
IS  - 1662-5102 (Print)
IS  - 1662-5102 (Electronic)
IS  - 1662-5102 (Linking)
VI  - 12
DP  - 2018
TI  - Inhibition of Connexin 43 Hemichannels Alleviates Cerebral Ischemia/Reperfusion 
      Injury via the TLR4 Signaling Pathway.
PG  - 372
LID - 10.3389/fncel.2018.00372 [doi]
LID - 372
AB  - Connexin 43 (Cx43) widely exists in all components of the neurovascular unit 
      (NVU) and is a constituent of gap junctions and hemichannels. In physiological 
      states, gap junctions are open for regular intercellular communication, and the 
      hemichannels present low open probability in astrocytes. After cerebral ischemia, 
      a large number of hemichannels are unusually opened, leading to cell swelling and 
      even death. Most known hemichannel blockers also inhibit gap junctions and 
      sequentially obstruct normal electrical cell-cell communication. In this study, 
      we tested the hypothesis that Gap19, a selective Cx43-hemichannel inhibitor, 
      exhibited neuroprotective effects on cerebral ischemia/reperfusion (I/R). An 
      obvious improvement in neurological scores and infarct volume reduction were 
      observed in Gap19-treated mice after brain ischemia induced by middle cerebral 
      artery occlusion (MCAO). Gap19 treatment attenuated white matter damage. 
      Moreover, Gap19 treatment suppressed the expression of Cx43 and Toll-like 
      receptor 4 (TLR4) pathway-relevant proteins and prevented the overexpression of 
      tumour necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta). To further explore 
      downstream signaling, we established an in vitro model-oxygen glucose deprivation 
      (OGD) to simulate ischemic conditions. Immunofluorescence staining showed that 
      Cx43 co-existed with TLR4 in astrocytes. The hemichannel activity was increased 
      after OGD and Gap19 could inhibit this effect on astrocytes. Gap19 substantially 
      improved relative cell vitality and decreased the expression of Cx43, TLR4 and 
      inflammatory cytokines in vitro. In addition, in the lipopolysaccharide (LPS) 
      stimulation OGD model, Gap19 also exhibited a protective effect via inhibiting 
      TLR4 pathway activation. In summary, our results showed that Gap19 exerted a 
      neuroprotective effect after stroke via inhibition of the TLR4-mediated signaling 
      pathway.
FAU - Chen, Yingzhu
AU  - Chen Y
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
FAU - Wang, Liangzhu
AU  - Wang L
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
AD  - Dalian Medical University, Dalian, China.
FAU - Zhang, Lingling
AU  - Zhang L
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
FAU - Chen, Beilei
AU  - Chen B
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
FAU - Yang, Liu
AU  - Yang L
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
AD  - Dalian Medical University, Dalian, China.
FAU - Li, Xiaobo
AU  - Li X
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
AD  - Institute of Neuroscience, Northern Jiangsu People's Hospital, Yangzhou, China.
FAU - Li, Yuping
AU  - Li Y
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
FAU - Yu, Hailong
AU  - Yu H
AD  - Clinical Medical College of Yangzhou University, Yangzhou, China.
AD  - Department of Neurology, Northern Jiangsu People's Hospital, Yangzhou, China.
AD  - Institute of Neuroscience, Northern Jiangsu People's Hospital, Yangzhou, China.
AD  - Drum Tower Hospital, Medical School of Nanjing University, Nanjing, China.
LA  - eng
PT  - Journal Article
DEP - 20181017
PL  - Switzerland
TA  - Front Cell Neurosci
JT  - Frontiers in cellular neuroscience
JID - 101477935
PMC - PMC6199357
OTO - NOTNLM
OT  - cerebral ischemia/reperfusion
OT  - hemichannel
OT  - inflammation
OT  - neuroprotection
OT  - neurovascular unit
OT  - toll-like receptor 4
EDAT- 2018/11/06 06:00
MHDA- 2018/11/06 06:01
PMCR- 2018/01/01
CRDT- 2018/11/03 06:00
PHST- 2018/05/30 00:00 [received]
PHST- 2018/09/28 00:00 [accepted]
PHST- 2018/11/03 06:00 [entrez]
PHST- 2018/11/06 06:00 [pubmed]
PHST- 2018/11/06 06:01 [medline]
PHST- 2018/01/01 00:00 [pmc-release]
AID - 10.3389/fncel.2018.00372 [doi]
PST - epublish
SO  - Front Cell Neurosci. 2018 Oct 17;12:372. doi: 10.3389/fncel.2018.00372. 
      eCollection 2018.