The dynamic blood-brain barrier

FEBS J. 2015 Nov;282(21):4067-79. doi: 10.1111/febs.13412. Epub 2015 Sep 8.


With the endothelium as its central unit, the blood-brain barrier (BBB) is a complex multicellular structure separating the central nervous system (CNS) from the systemic circulation. Disruption of the BBB has now been implicated in a multitude of acute and chronic CNS disorders indicating the potentially devastating effects of BBB breakdown on brain function. However, the healthy BBB is not an impermeable wall, but rather a communication 'centre', responding to and passing signals between the CNS and blood. New studies are identifying BBB-specific transport pathways that tightly regulate the entry and exit of molecules to and from the brain. They are revealing a highly plastic barrier in which dynamic changes in BBB components like paracellular tight junction complexes can contribute to BBB maintenance. Here, we provide a succinct overview of the current state-of-play in BBB research and summarize novel findings into BBB regulation in homeostatic regulation of the brain.

Keywords: Alzheimer's disease; GLUT-1; Mfsd2a; astrocytes; blood-brain barrier; gut microbiota; neurovascular unit; pericytes; tight junctions; transcytosis.

Publication types

  • Review

MeSH terms

  • Aging / physiology
  • Alzheimer Disease / physiopathology
  • Amyloid beta-Peptides / physiology
  • Animals
  • Astrocytes / physiology
  • Basement Membrane / physiology
  • Blood-Brain Barrier / immunology
  • Blood-Brain Barrier / physiology*
  • Brain / blood supply
  • Brain / cytology
  • Brain / physiology
  • Central Nervous System Diseases / physiopathology
  • Endothelium, Vascular / physiology
  • Gastrointestinal Microbiome / physiology
  • Glucose Transporter Type 1 / physiology
  • Humans
  • Immunity, Innate
  • Microglia / physiology
  • Pericytes / physiology
  • Sleep / physiology
  • Stroke / physiopathology
  • Symporters
  • Tight Junctions / physiology
  • Transcytosis
  • Tumor Suppressor Proteins / genetics
  • Tumor Suppressor Proteins / physiology


  • Amyloid beta-Peptides
  • Glucose Transporter Type 1
  • MFSD2A protein, human
  • Symporters
  • Tumor Suppressor Proteins