PMID- 38377019
OWN - NLM
STAT- Publisher
LR  - 20240220
IS  - 2152-5250 (Electronic)
IS  - 2152-5250 (Linking)
DP  - 2024 Feb 9
TI  - Neuron Derived Cold-Inducible RNA-Binding Protein Promotes NETs Formation to 
      Exacerbate Brain Endothelial Barrier Disruption after Ischemic Stroke.
LID - 10.14336/AD.2024.0204-1 [doi]
AB  - In ischemic stroke, neutrophils are the first-line peripheral immune cells 
      infiltrating the brain tissue to form neutrophil extracellular traps (NETs). The 
      present study aimed to investigate the role of neuronal cold-inducible 
      RNA-binding protein (CIRP) in promoting NETs-induced brain endothelial barrier 
      destruction and cerebral edema after ischemic stroke. We found that the 
      expression of NETs and neuronal CIRP in the penumbra increased at 6 hours after 
      transient middle cerebral artery occlusion (tMCAO) and increased significantly at 
      24 hours, reaching a peak at 3 days. NETs degradation or CIRP inhibition can 
      alleviate the leakage of brain endothelial barrier and reverse the decreased 
      expression of tight junction proteins (zonula occludens-1, claudin-5 and 
      occludin) in tMCAO mice. Oxygen-glucose deprivation/reperfusion treated primary 
      neurons or recombinant CIRP could induce NETs formation via TLR4/p38 signaling 
      pathway in vitro. Transcription factor specificity protein 1 (sp1) was 
      responsible for the increased neuronal CIRP expression and the inhibition of sp1 
      could suppress the increased CIRP expression, reduce NETs formation, and diminish 
      brain endothelial barrier leakage in tMCAO mice. We also found the upregulated 
      CIRP level was associated with severe cerebral edema in patients with acute 
      ischemic stroke. In conclusion, the increased expression of transcription factor 
      sp1 after ischemic stroke can lead to elevated CIRP expression and release from 
      the neurons, which subsequently interacts with neutrophils and promotes NETs 
      formation, resulting in brain endothelial barrier destruction and cerebral edema.
FAU - Li, Zhifang
AU  - Li Z
FAU - Sun, Shuai
AU  - Sun S
FAU - Xiao, Qinghui
AU  - Xiao Q
FAU - Tan, Senwei
AU  - Tan S
FAU - Jin, Huijuan
AU  - Jin H
FAU - Hu, Bo
AU  - Hu B
LA  - eng
PT  - Journal Article
DEP - 20240209
PL  - United States
TA  - Aging Dis
JT  - Aging and disease
JID - 101540533
SB  - IM
EDAT- 2024/02/20 18:42
MHDA- 2024/02/20 18:42
CRDT- 2024/02/20 12:53
PHST- 2023/10/19 00:00 [received]
PHST- 2024/02/04 00:00 [accepted]
PHST- 2024/02/20 18:42 [medline]
PHST- 2024/02/20 18:42 [pubmed]
PHST- 2024/02/20 12:53 [entrez]
AID - AD.2024.0204-1 [pii]
AID - 10.14336/AD.2024.0204-1 [doi]
PST - aheadofprint
SO  - Aging Dis. 2024 Feb 9. doi: 10.14336/AD.2024.0204-1.