Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module.
Animals
Biotin
/ metabolism
Blood-Brain Barrier
/ metabolism
Brain
/ metabolism
Brain Injuries, Traumatic
/ metabolism
Endothelial Cells
/ metabolism
Infarction, Middle Cerebral Artery
Kainic Acid
Mice
Mice, Transgenic
Multiple Sclerosis
/ chemically induced
Myelin-Oligodendrocyte Glycoprotein
Peptide Fragments
Permeability
Pertussis Toxin
Seizures
/ chemically induced
Signal Transduction
Stroke
/ metabolism
Transcriptome
/ genetics
Journal
Nature neuroscience
ISSN: 1546-1726
Titre abrégé: Nat Neurosci
Pays: United States
ID NLM: 9809671
Informations de publication
Date de publication:
11 2019
11 2019
Historique:
received:
11
02
2019
accepted:
13
08
2019
pubmed:
16
10
2019
medline:
1
2
2020
entrez:
16
10
2019
Statut:
ppublish
Résumé
Blood vessels in the CNS form a specialized and critical structure, the blood-brain barrier (BBB). We present a resource to understand the molecular mechanisms that regulate BBB function in health and dysfunction during disease. Using endothelial cell enrichment and RNA sequencing, we analyzed the gene expression of endothelial cells in mice, comparing brain endothelial cells with peripheral endothelial cells. We also assessed the regulation of CNS endothelial gene expression in models of stroke, multiple sclerosis, traumatic brain injury and seizure, each having profound BBB disruption. We found that although each is caused by a distinct trigger, they exhibit strikingly similar endothelial gene expression changes during BBB disruption, comprising a core BBB dysfunction module that shifts the CNS endothelial cells into a peripheral endothelial cell-like state. The identification of a common pathway for BBB dysfunction suggests that targeting therapeutic agents to limit it may be effective across multiple neurological disorders.
Identifiants
pubmed: 31611708
doi: 10.1038/s41593-019-0497-x
pii: 10.1038/s41593-019-0497-x
pmc: PMC6858546
mid: NIHMS1537438
doi:
Substances chimiques
Myelin-Oligodendrocyte Glycoprotein
0
Peptide Fragments
0
myelin oligodendrocyte glycoprotein (35-50), Ala(37)-
0
Biotin
6SO6U10H04
Pertussis Toxin
EC 2.4.2.31
Kainic Acid
SIV03811UC
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1892-1902Subventions
Organisme : NINDS NIH HHS
ID : R01 NS091281
Pays : United States
Organisme : NCI NIH HHS
ID : T32 CA151022
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS055876
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH113896
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS050159
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007546
Pays : United States
Organisme : NCI NIH HHS
ID : P50 CA097257
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS077767
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS082280
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008440
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM007198
Pays : United States
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