Pericytes

Pericytes are vascular mural cells embedded in the basement membrane of blood microvessels. They extend their processes along capillaries, pre-capillary arterioles and post-capillary venules. Pericytes regulate blood-brain barrier (BBB) permeability, angiogenesis, clearance, cerebral blood flow (CBF), neuroinflammation and stem cell activity.

BBB permeability

Pericytes control the expression of endothelial BBB tight and adherens junction proteins, the alignment of tight junction proteins and bulk-flow transcytosis of fluid-filled vesicles across the BBB. Molecular pathways between pericytes and endothelial cells can be manipulated to open the BBB 'on demand' for neuropharmaceutical delivery and/or to reverse BBB disruption in neurological diseases.

Angiogenesis

Pericytes regulate angiogenesis, microvascular stability and angioarchitecture during CNS development and vascular remodeling.

Clearance

Pericytes can also act as perivascular tissue macrophages to clear tissue debris and foreign proteins injected systemically and/or locally into the CNS and participate in clearance of Alzheimer's amyloid-β toxin, as shown in a mouse Alzheimer's disease model.

CBF

The mammalian brain has evolved a regional control mechanism for CBF, known as neurovascular coupling, which ensures a rapid increase in the amount of CBF directed to active neurons. Neurovascular coupling is controlled by cells within the neurovascular unit, including pericytes. Pericytes can actively relax or contract to change CBF in response to localized changes in neuronal activity.

Neuroinflammation

Pericytes are able to recruit immune cells and enable their extravasation into the brain. In transgenic pericyte-deficient mice, there is reduced leukocyte trafficking across the microvasculature, suggesting a role for pericytes in leukocyte recruitment to the brain.

Stem cell activity

In vitro studies have shown that cultured pericytes have pluripotent stem cell potential. Furthermore, mouse primary pericytes isolated from brain following ischemic stroke exhibit pluripotential stem cell activity and differentiate into neural and vascular lineage cells. The exact mediators that control pericyte differentiation are still under investigation, but pericyte pluripotency can be used as a target for therapeutic intervention for a number of diseases.