Profiling the mouse brain endothelial transcriptome in health and disease models reveals a core blood-brain barrier dysfunction module

Nat Neurosci. 2019 Nov;22(11):1892-1902. doi: 10.1038/s41593-019-0497-x. Epub 2019 Oct 14.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • 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
  • Multiple Sclerosis / metabolism*
  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • Permeability
  • Pertussis Toxin
  • Seizures / chemically induced
  • Seizures / metabolism*
  • Signal Transduction
  • Stroke / metabolism*
  • Transcriptome / genetics*


  • Myelin-Oligodendrocyte Glycoprotein
  • Peptide Fragments
  • myelin oligodendrocyte glycoprotein (35-50), Ala(37)-
  • Biotin
  • Pertussis Toxin
  • Kainic Acid