Abstract
Central nervous system (CNS) injuries are the most common cause of death and disability around the world. The blood-brain barrier (BBB) is located at the interface between the CNS and the surrounding environment, which protects the CNS from exogenous molecules, harmful agents or microorganisms in the blood. The disruption of BBB is a common feature of CNS injuries and participates in the pathological processes of secondary brain damage. Recently, a growing number of studies have indicated that non-coding RNAs (ncRNAs) play an important role in brain development and are involved in CNS injuries. In this review, we summarize the mechanisms of BBB breakdown after CNS injuries. We also discuss the effects of ncRNAs including long noncoding RNAs (lncRNAs), circular RNAs (circRNAs) and microRNAs (miRNAs) on BBB damage in CNS injuries such as ischemic stroke, traumatic brain injury (TBI), intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH). In addition, we clarify the pharmacotherapies that could regulate BBB function via ncRNAs in CNS injuries, as well as the challenges and perspectives of ncRNAs on modulation of BBB function. Hence, on the basis of these effects, ncRNAs may be developed as therapeutic agents to protect the BBB for CNS injury patients.
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Data Availability
All data generated during this review are included in this article.
Abbreviations
- ANO1:
-
anoctamin-1
- Ang-1:
-
Angiopoietin-1
- ANRIL:
-
antisense noncoding RNA in the INK4 locus
- ARF3:
-
adenosine diphosphate-ribosylation factor 3
- BBB:
-
blood-brain barrier
- Blnc1:
-
brown fat enriched lncRNA 1
- BMECs:
-
brain microvascular endothelial cells
- BMAL1:
-
brain and muscle ARNT-like protein-1
- CAMs:
-
cell adhesion molecules
- circRNA:
-
circular RNA
- CTNNB1:
-
catenin beta 1
- CNS:
-
central nervous system
- DLGAP4:
-
Disc large associated protein 4
- DUSP8:
-
dual-specificity phosphatase 8
- E2F1:
-
E2F transcription factor 1
- FGD5-AS1:
-
FGD5 antisense RNA 1
- FoxO3:
-
forkhead box O3
- HDAC3:
-
histone deacetylase 3
- HIE:
-
hypoxic-ischemic encephalopathy
- IRAK1:
-
interleukin-1 receptor associated kinase 1
- HMGB1:
-
high-mobility group box 1 protein
- HMGA2:
-
high mobility group A2
- ICH:
-
intracerebral hemorrhage
- Itgα5:
-
integrin α5
- lncRNA:
-
long noncoding RNA
- MAPK:
-
mitogen-activated protein kinase
- MAT2B:
-
methionine adenosyltransferase 2B
- MT2:
-
metallothionein-2
- MEG3:
-
maternally expressed gene 3
- miRNA:
-
microRNA
- MMP-9:
-
matrix metalloproteinase-9
- mTOR:
-
mammalian target of rapamycin
- MyD88:
-
myeloid differentiation factor 88
- ncRNAs:
-
non-coding ribonucleic acids
- NF-κB:
-
nuclear factor-κB
- NKILA:
-
NF-κB interacting lncRNA
- Nrf2:
-
nuclear factor erythroid 2-related factor 2
- NLRP3:
-
NOD-like receptor family pyrin domain containing 3
- PIK3R2:
-
phosphoinositide-3-kinase regulatory subunit 2
- PPAR-γ:
-
peroxisome proliferator-activated receptor-γ
- Ptpn14:
-
protein tyrosine phosphatase non-receptor type 14
- S1PR2:
-
sphingosine-1-phosphate receptor
- SIRT6:
-
sirtuin 6
- SNHG8:
-
small nucleolar RNA host gene 8
- SEMA3A:
-
semaphorin 3 A
- SRB1:
-
scavenger receptor class B type 1
- SOX7:
-
SRY-box transcription factor 7
- TBI:
-
traumatic brain injury
- TJ:
-
tight junction
- TLR4:
-
toll-like receptor-4
- TRAF6:
-
tumor necrosis factor receptor-associated factor 6
- TIMP3:
-
tissue inhibitor of metalloproteinase-3
- VCAM-1:
-
vascular cell adhesion molecule-1
- VEGFA:
-
vascular endothelial growth factor-A
- XIST:
-
X-inactive-specific transcript
- ZEB2:
-
zinc finger E-box-binding homeobox 2
- 5-LOX:
-
5-lipoxygenase
- NVU:
-
neurovascular unit
- AJs:
-
adherens junctions
- Zos:
-
zonula occludins
- JAMs:
-
junctional adhesion molecules
- ICAM-1:
-
intercellular adhesion molecule-1
- VCAM-1:
-
vascular cell adhesion molecule-1
- TNF-α:
-
tumor necrosis factor-α
- IL-1β:
-
interleukin-1β
- IL-6:
-
interleukin-6
- TGF-β:
-
transforming growth factor-β
- AKT:
-
protein kinase B
- CREB:
-
cyclic adenosine 3’,5’-monophosphate responsive element-binding protein
- BDNF:
-
brain-derived neurotrophic factor
- Gas6:
-
growth arrest-specific 6
- MCAO:
-
middle cerebral artery occlusion
- HDAC3:
-
histone deacetylase 3
- AQP4:
-
aquaporin-4
- ROS:
-
reactive oxygen species
- PFA:
-
polyunsaturated fatty acids
- NADPH:
-
nicotinamide adenine dinucleotide phosphate
- SOD:
-
superoxide dismutase
- GSH-Px:
-
glutathione peroxidase
- 8-OHdG:
-
8-hydroxy-2-deoxyguanosine
- I/R:
-
ischemia/reperfusion
- CAT:
-
catalase
- PGK1:
-
phosphoglycerate kinase 1
- HO-1:
-
heme oxygenase-1
- Mfsd2a:
-
major facilitator superfamily domain containing 2a
- SAC:
-
salvianolic acid C
- Ang1:
-
angiopoietin 1
- CCI:
-
controlled cortical impact
- Bcl-2:
-
B-cell lymphoma 2
- Bax:
-
Bcl-2 associated x protein
- TUNEL:
-
TdT-mediated dUTP Nick-End Labeling
- ceRNAs:
-
competing endogenous RNAs
- OGD/R:
-
oxygen-glucose deprivation/reoxygenation
- GSDMD:
-
Gasdermin D
- BACH1:
-
BTB and CNC homology 1
- PTEN:
-
phosphatase and tensin homolog deleted on chromosome 10
- α-SMA:
-
α-smooth muscle actin
- NIHSS:
-
National Institute of Health Stroke Scale
- vWF:
-
von Willebrand factor
- rhFGF20:
-
recombinant human fibroblast growth factor 20
- TEER:
-
trans endothelial electrical resistance
- C1QTNF6:
-
C1q and TNF-related 6
- ZEB2:
-
zinc finger E-box-binding homeobox 2
- STING:
-
stimulator of interferon gene
- CLP:
-
cecal ligation and perforation
- IgG:
-
immunoglobulin G
- 3’-UTR:
-
3’-untranslated region
- COX-2:
-
cyclooxygenase-2
- MCP-1:
-
monocyte chemoattractant protein-1
- STAT3:
-
signal transducers and activators of transcription 3
- MVEs:
-
multi-vesicle endosomes
- BMSCs:
-
bone marrow mesenchymal stem cells
- H/R:
-
hypoxia/reoxygenation
- NPs:
-
nanoparticles
- PEG:
-
polyethylene glycol
- AAV:
-
adeno-associated virus
- sh:
-
short hairpin.
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This work was supported by Grants from the National Natural Science Foundation of China (No. 82202392) to Mi Tian.
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Li Zhang was responsible for the manuscript writing including figures; Wanshan Bai was responsible for the literature collection and manuscript review; Lean Sun was responsible for the tables; Yixing Lin was responsible for the whole work design; Mi Tian was responsible for paper submission and funding support. All authors read and approved the final manuscript.
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Zhang, L., Bai, W., Sun, L. et al. Targeting Non-Coding RNA for CNS Injuries: Regulation of Blood-Brain Barrier Functions. Neurochem Res 48, 1997–2016 (2023). https://doi.org/10.1007/s11064-023-03892-1
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DOI: https://doi.org/10.1007/s11064-023-03892-1