The CNS microvascular pericyte: pericyte-astrocyte crosstalk in the regulation of tissue survival

Abstract

The French scientist Charles Benjamin Rouget identified the pericyte nearly 140 years ago. Since that time the role of the pericyte in vascular function has been difficult to elucidate. It was not until the development of techniques to isolate and culture pericytes that scientists have begun to understand the true impact of this unique cell in the maintenance of tissue homeostasis. In the brain the pericyte is an integral cellular component of the blood-brain barrier and, together with other cells of the neurovascular unit (endothelial cells, astrocytes and neurons) the pericyte makes fine-tuned regulatory adjustments and adaptations to promote tissue survival. These regulatory changes involve trans-cellular communication networks between cells. In this review we consider evidence for cell-to-cell crosstalk between pericytes and astrocytes during development and in adult brain.

Figure 1

Induction of angiogenesis in triple co-cultures of ECs, pericytes and astrocytes. Primary cells were co-cultured at a ratio of one pericyte to five ECs and to five astrocytes. Cultures were exposed to hypoxia (10%) to induce angiogenesis (A). Tube formation in triple cultures involved crosstalk between astrocytes and pericytes. White arrows point to pericytes and black arrows point to astrocytes. Photograph was taken using phase contrast at 10×. In (B) we show a close up of an astrocyte making contact with both elongating EC and pericytes. The black arrows point to astrocyte contacts with an elongating EC (left) and one of the two contacts made with a pericyte (right). Pericytes have fewer projections and are more spread out than the astrocytes.

Figure 2

Capillaries [2-6 micron diameter determined by Image J software] were isolated from wild type C57BL/6 mice (A), GFAP -/+ mice (B), and GFAP -/- mice (C) (Jackson Laboratory). Freshly isolated capillaries were allowed to adhere to coverslips fixed and stained for the expression of GFAP (Santa Cruz Biotechnology Inc). Capillaries were visualized on a Leitz fluorescent microscope at 40× and 100×.

Figure 3

Pericyte-endothelial cell ratios were determined by isolation of capillaries [2-4 micron diameter determined by Image J software] from wild type B6 mice (A); heterozygous GFAP -/+ mice (B) and knockout GFAP -/- mice (C). Freshly isolated capillaries were stained with the fluorescent nuclear dye 4',6-diamidino-2-phenylindole [DAPI]. Round nuclei (pericytes) and elongated nuclei (EC) were counted. Numbers are shown in Table 1. Arrows point to round pericyte nuclei.