Pericytes regulate the blood–brain barrier

  title={Pericytes regulate the blood–brain barrier},
  author={Annika Armulik and Guillem Genov{\'e} and Maarja Andaloussi M{\"a}e and Maya H. Nisancioglu and Elisabet Wallgard and C. Niaudet and Liqun He and Jenny M. Norlin and Per Lindblom and Karin Strittmatter and Bengt R. Johansson and Christer Betsholtz},
The blood–brain barrier (BBB) consists of specific physical barriers, enzymes and transporters, which together maintain the necessary extracellular environment of the central nervous system (CNS. [] Key Result Using a set of adult viable pericyte-deficient mouse mutants we show that pericyte deficiency increases the permeability of the BBB to water and a range of low-molecular-mass and high-molecular-mass tracers.

Region-specific permeability of the blood–brain barrier upon pericyte loss

It is shown that BBB permeability is heterogeneous in pdgf-b ret/ret mice, being significantly higher in the cortex, striatum and hippocampus compared to the interbrain and midbrain, and it is suggested that additional, locally-acting mechanisms may contribute to control of transport.

Tight junctions at the blood brain barrier: physiological architecture and disease-associated dysregulation

Current understanding of the structure and functional regulation of endothelial TJs at the BBB is summarized, pointing to a correlation between BBB dysfunction, alteration of TJ complexes and progression of a variety of CNS diseases, such as stroke, multiple sclerosis and brain tumors, as well as neurodegenerative diseases like Parkinson's and Alzheimer’s diseases.

Transcytosis at the blood–brain barrier

Novel insights into the development and maintenance of the blood–brain barrier

The currently known cellular and molecular mechanisms mediating brain angiogenesis are summarized and more recently discovered CNS-specific pathways and molecules that are crucial in BBB differentiation and maturation are introduced.

Macrophages Enforce the Blood Nerve Barrier

It is found that while ECs of the PNS have higher transcytosis rates than those of the CNS, the barrier is reinforced by resident macrophages that specifically engulf leaked material, identifying a distinct role for macrophage as an important component of the BNB acting to protect the P NS environment with implications for improving therapeutic delivery to this tissue.

Modelling the neurovascular unit and the blood-brain barrier with the unique function of pericytes.

Two different three-cell-type culture models were described, including pericytes to mimic the neurovascular unit and low paracellular permeability and P-glycoprotein functionality were demonstrated, likely to be useful tools for understanding the pericyte's role in BBB physiology.

Current concepts of blood-brain barrier development.

Developmental aspects of the blood-brain barrier are focused on and morphological as well as molecular special features of the neuro-vascular unit (NVU) involved in barrier induction are described.

Vascular and perivascular cell profiling reveals the molecular and cellular bases of blood-brain barrier heterogeneity

Differences in ECs, together with region-specific physical and molecular interactions with local perivascular cells, contribute to BBB functional heterogeneity, and regional specialization of the BBB is achieved.

The effect of chemokines on brain endothelial cell function

Results indicate that that these chemokines may contribute to the opening of the BBB and the pathogenesis of neuroinflammatory diseases.

Pericytes: brain-immune interface modulators

Better understanding of the immune properties of pericytes and their participation in the effects of brain infections, neurodegenerative diseases, and sleep loss will be achieved by analyzing pericyte ultrastructure, capillary coverage, and protein expression.



Physiology and pharmacological role of the blood-brain barrier.

The blood-brain barrier is the most significant element responsible for the preservation of CNS homeostasis and can be investigated as a functional system as a frontier composed of pericytes, astrocytic end feet, and brain endothelial cells (ECs).

Astrocytes induce blood–brain barrier properties in endothelial cells

Direct evidence is provided that astrocytes are capable of inducing blood–brain barrier properties in non-neural endothelial cells in vivo.

Agrin, Aquaporin-4, and Astrocyte Polarity as an Important Feature of the Blood-Brain Barrier

The role of astroglial cells in managing theBBB and aspects of pathological alterations in the brain as far as the BBB is involved are discussed and both the structure and function of the brain capillary endothelial cells are described.

Astrocyte–endothelial interactions at the blood–brain barrier

Specific interactions between the brain endothelium, astrocytes and neurons that may regulate blood–brain barrier function are explored to lead to the development of new protective and restorative therapies.

Wnt/β-catenin signaling controls development of the blood–brain barrier

Stabilization of β-cat in primary brain endothelial cells (ECs) in vitro by N-terminal truncation or Wnt3a treatment increases Cldn3 expression, BBB-type tight junction formation, and a BBB characteristic gene signature, and this findings may open new therapeutic avenues to modulate endothelial barrier function.

Induction of various blood‐brain barrier properties in non‐neural endothelial cells by close apposition to co‐cultured astrocytes

The results obtained with this heterologous co‐culture system indicate that through contact with their feet, astrocytes are capable of transdifferentiating non‐neural EC into the brain type, endowing them with the BBB properties.


These findings localize, at a fine structural level, a "barrier" to the passage of peroxidase at the endothelium of vessels in the cerebral cortex in mice, particularly with reference to a recent study in which similar techniques were applied to capillaries in heart and skeletal muscle.

Lack of Pericytes Leads to Endothelial Hyperplasia and Abnormal Vascular Morphogenesis

Although PC deficiency appears to have direct effects on EC number before E 13.5, the subsequent increased VEGF-A levels may further abrogate microvessel architecture, promote vascular permeability, and contribute to formation of the edematous phenotype observed in late gestation PDGF-B and PDGFR-beta knock out embryos.