PMID- 31779652
OWN - NLM
STAT- MEDLINE
DCOM- 20200514
LR  - 20200514
IS  - 1742-2094 (Electronic)
IS  - 1742-2094 (Linking)
VI  - 16
IP  - 1
DP  - 2019 Nov 28
TI  - The glucagon-like peptide-1 receptor agonist reduces inflammation and blood-brain 
      barrier breakdown in an astrocyte-dependent manner in experimental stroke.
PG  - 242
LID - 10.1186/s12974-019-1638-6 [doi]
LID - 242
AB  - BACKGROUND: Preserving the integrity of the blood-brain barrier (BBB) is 
      beneficial to avoid further brain damage after acute ischemic stroke (AIS). 
      Astrocytes, an important component of the BBB, promote BBB breakdown in subjects 
      with AIS by secreting inflammatory factors. The glucagon-like peptide-1 receptor 
      (GLP-1R) agonist exendin-4 (Ex-4) protects the BBB and reduces brain inflammation 
      from cerebral ischemia, and GLP-1R is expressed on astrocytes. However, the 
      effect of Ex-4 on astrocytes in subjects with AIS remains unclear. METHODS: In 
      the present study, we investigated the effect of Ex-4 on astrocytes cultured 
      under oxygen-glucose deprivation (OGD) plus reoxygenation conditions and 
      determined whether the effect influences bEnd.3 cells. We used various methods, 
      including permeability assays, western blotting, immunofluorescence staining, and 
      gelatin zymography, in vitro and in vivo. RESULTS: Ex-4 reduced OGD-induced 
      astrocyte-derived vascular endothelial growth factor (VEGF-A), matrix 
      metalloproteinase-9 (MMP-9), chemokine monocyte chemoattractant protein-1 
      (MCP-1), and chemokine C-X-C motif ligand 1 (CXCL-1). The reduction in 
      astrocyte-derived VEGF-A and MMP-9 was related to the increased expression of 
      tight junction proteins (TJPs) in bEnd.3 cells. Ex-4 improved neurologic deficit 
      scores, reduced the infarct area, and ameliorated BBB breakdown as well as 
      decreased astrocyte-derived VEGF-A, MMP-9, CXCL-1, and MCP-1 levels in ischemic 
      brain tissues from rats subjected to middle cerebral artery occlusion. Ex-4 
      reduced the activation of the JAK2/STAT3 signaling pathway in astrocytes 
      following OGD. CONCLUSION: Based on these findings, ischemia-induced inflammation 
      and BBB breakdown can be improved by Ex-4 through an astrocyte-dependent manner.
FAU - Shan, Yilong
AU  - Shan Y
AD  - Department of Rehabilitation Medicine, The Third Affiliated Hospital of Sun 
      Yat-sen University, No. 600 Tianhe Road, Guangzhou City, China.
FAU - Tan, Sha
AU  - Tan S
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Lin, Yinyao
AU  - Lin Y
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Liao, Siyuan
AU  - Liao S
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Zhang, Bingjun
AU  - Zhang B
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Chen, Xiaodong
AU  - Chen X
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Wang, Jihui
AU  - Wang J
AD  - Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen 
      University, No. 600 Tianhe Road, Guangzhou City, China.
FAU - Deng, Zhezhi
AU  - Deng Z
AD  - Department of Psychiatry, The Third Affiliated Hospital of Sun Yat-sen 
      University, No. 600 Tianhe Road, Guangzhou City, China.
FAU - Zeng, Qin
AU  - Zeng Q
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Zhang, Lei
AU  - Zhang L
AD  - Department of Neurology, The Fifth Affiliated Hospital of Sun Yat-sen University, 
      No. 52 Meihuadong Road, Zhuhai City, China.
FAU - Wang, Yuge
AU  - Wang Y
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Hu, Xueqiang
AU  - Hu X
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Qiu, Wei
AU  - Qiu W
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Peng, Lisheng
AU  - Peng L
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China.
FAU - Lu, Zhengqi
AU  - Lu Z
AD  - Department of Neurology, The Third Affiliated Hospital of Sun Yat-sen University, 
      No. 600 Tianhe Road, Guangzhou City, China. lzq1828@163.com.
LA  - eng
GR  - 81671178/National Natural Science Foundation of China/
GR  - 2017A030311013/Natural Science Foundation of Guangdong Province/
PT  - Journal Article
DEP - 20191128
PL  - England
TA  - J Neuroinflammation
JT  - Journal of neuroinflammation
JID - 101222974
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chemokine CXCL1)
RN  - 0 (Glucagon-Like Peptide-1 Receptor)
RN  - 0 (Vascular Endothelial Growth Factor A)
RN  - 9P1872D4OL (Exenatide)
RN  - EC 3.4.24.35 (Matrix Metalloproteinase 9)
SB  - IM
MH  - Animals
MH  - Astrocytes/*drug effects/metabolism
MH  - Blood-Brain Barrier/*drug effects/pathology
MH  - Chemokine CCL2/metabolism
MH  - Chemokine CXCL1/metabolism
MH  - Exenatide/*pharmacology/therapeutic use
MH  - Glucagon-Like Peptide-1 Receptor/*agonists
MH  - Infarction, Middle Cerebral Artery/*metabolism/pathology
MH  - Inflammation/*drug therapy/metabolism/pathology
MH  - Male
MH  - Matrix Metalloproteinase 9/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Stroke/*metabolism/pathology
MH  - Vascular Endothelial Growth Factor A/metabolism
PMC - PMC6883580
OTO - NOTNLM
OT  - Astrocyte
OT  - Blood-brain barrier
OT  - Exendin-4
OT  - Ischemic stroke
OT  - Oxygen-glucose deprivation
COIS- The authors declare that they have no competing interests.
EDAT- 2019/11/30 06:00
MHDA- 2020/05/15 06:00
PMCR- 2019/11/28
CRDT- 2019/11/30 06:00
PHST- 2018/12/04 00:00 [received]
PHST- 2019/11/11 00:00 [accepted]
PHST- 2019/11/30 06:00 [entrez]
PHST- 2019/11/30 06:00 [pubmed]
PHST- 2020/05/15 06:00 [medline]
PHST- 2019/11/28 00:00 [pmc-release]
AID - 10.1186/s12974-019-1638-6 [pii]
AID - 1638 [pii]
AID - 10.1186/s12974-019-1638-6 [doi]
PST - epublish
SO  - J Neuroinflammation. 2019 Nov 28;16(1):242. doi: 10.1186/s12974-019-1638-6.