PMID- 33390799
OWN - NLM
STAT- MEDLINE
DCOM- 20210913
LR  - 20210913
IS  - 1449-1907 (Electronic)
IS  - 1449-1907 (Linking)
VI  - 18
IP  - 2
DP  - 2021
TI  - FTY720 Reduces Endothelial Cell Apoptosis and Remodels Neurovascular Unit after 
      Experimental Traumatic Brain Injury.
PG  - 304-313
LID - 10.7150/ijms.49066 [doi]
AB  - Traumatic brain injury (TBI) is a major cause of death and disability worldwide. 
      A sequence of pathological processes occurred when there is TBI. Previous studies 
      showed that sphingosine-1-phosphate receptor 1 (S1PR1) played a critical role in 
      inflammatory response in the brain after TBI. Thus, the present study was 
      designed to evaluate the effects of the S1PR1 modulator FTY720 on neurovascular 
      unit (NVU) after experimental TBI in mice. The weight-drop TBI method was used to 
      induce TBI. Western blot (WB) was performed to determine the levels of SIPR1, 
      claudin-5 and occludin at different time points. FTY720 was intraperitoneally 
      administered to mice after TBI was induced. The terminal deoxynucleotidyl 
      transferase-dUTP nick end labeling (TUNEL) assay was used to assess endothelial 
      cell apoptosis. Immunofluorescence and WB were performed to measure the 
      expression of tight junction proteins: claudin-5 and occludin. Evans blue (EB) 
      permeability assay and brain water content were applied to evaluate the 
      blood-brain barrier (BBB) permeability and brain edema. Immunohistochemistry was 
      performed to assess the activation of astrocytes and microglia. The results 
      showed that FTY720 administration reduced endothelial cell apoptosis and improved 
      BBB permeability. FTY720 also attenuated astrocytes and microglia activation. 
      Furthermore, treatment with FTY720 not only improved neurological function, but 
      also increased the survival rate of mice significantly. These findings suggest 
      that FTY720 administration restored the structure of the NVU after experimental 
      TBI by decreasing endothelial cell apoptosis and attenuating the activation of 
      astrocytes. Moreover, FTY720 might reduce inflammation in the brain by reducing 
      the activation of microglia in TBI mice.
CI  - (c) The author(s).
FAU - Cheng, Hao
AU  - Cheng H
AD  - Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Anhui, 
      China.
FAU - Di, Guangfu
AU  - Di G
AD  - Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Anhui, 
      China.
FAU - Gao, Chao-Chao
AU  - Gao CC
AD  - Department of Neurosurgery, Jinling Hospital, Jinling School of Clinical 
      Medicine, Nanjing Medical University, Jiangsu, China.
FAU - He, Guoyuan
AU  - He G
AD  - Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Anhui, 
      China.
FAU - Wang, Xue
AU  - Wang X
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Jiangsu, China.
FAU - Han, Yan-Ling
AU  - Han YL
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Jiangsu, China.
FAU - Sun, Le-An
AU  - Sun LA
AD  - Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Anhui, 
      China.
FAU - Zhou, Meng-Liang
AU  - Zhou ML
AD  - Department of Neurosurgery, Jinling Hospital, School of Medicine, Nanjing 
      University, Jiangsu, China.
FAU - Jiang, Xiaochun
AU  - Jiang X
AD  - Department of Neurosurgery, Yijishan Hospital, Wannan Medical College, Anhui, 
      China.
LA  - eng
PT  - Journal Article
DEP - 20210101
PL  - Australia
TA  - Int J Med Sci
JT  - International journal of medical sciences
JID - 101213954
RN  - G926EC510T (Fingolimod Hydrochloride)
SB  - IM
MH  - Animals
MH  - Apoptosis/drug effects
MH  - Astrocytes/*drug effects/pathology
MH  - Blood-Brain Barrier/cytology/*drug effects/pathology
MH  - Brain Injuries, Traumatic/*drug therapy/pathology
MH  - Capillary Permeability/drug effects
MH  - Disease Models, Animal
MH  - Endothelial Cells/*drug effects/pathology
MH  - Fingolimod Hydrochloride/*administration & dosage
MH  - Humans
MH  - Injections, Intraperitoneal
MH  - Mice
MH  - Mice, Inbred ICR
PMC - PMC7757143
OTO - NOTNLM
OT  - FTY720
OT  - blood-brain barrier
OT  - endothelial cell
OT  - sphingosine-1-phosphate receptor 1
OT  - traumatic brain injury
COIS- Competing Interests: The authors have declared that no competing interest exists.
EDAT- 2021/01/05 06:00
MHDA- 2021/09/14 06:00
PMCR- 2021/01/01
CRDT- 2021/01/04 05:25
PHST- 2020/06/03 00:00 [received]
PHST- 2020/11/05 00:00 [accepted]
PHST- 2021/01/04 05:25 [entrez]
PHST- 2021/01/05 06:00 [pubmed]
PHST- 2021/09/14 06:00 [medline]
PHST- 2021/01/01 00:00 [pmc-release]
AID - ijmsv18p0304 [pii]
AID - 10.7150/ijms.49066 [doi]
PST - epublish
SO  - Int J Med Sci. 2021 Jan 1;18(2):304-313. doi: 10.7150/ijms.49066. eCollection 
      2021.