Abstract

High Content Assays Measuring Human Brain Pericyte Biology

Mike Dragunow, Professor of Pharmacology, Auckland University

Brain pericytes are perivascular cells thought to play diverse roles in brain physiology and pathology. They have been implicated in the formation and maintenance of the blood-brain barrier and the functioning of the brain capillary network. Studies have also suggested that these cells may act as a vascular source of neural stem cells and play a role in neurogenesis. A loss of pericyte coverage of capillary beds has been implicated in BBB leakage in various brain disorders. Furthermore, brain pericytes may be involved in neuroinflammation and may be a source cell for the generation of myofibroblasts during tissue scarring. For these reasons the pericyte is potentially an important cellular target for the development of CNS acting drugs to treat a range of brain disorders. We have developed high content assays to measure various features of human brain pericytes for drug screening purposes. We will describe a nested assay which measures basal expression of the chemokine MCP-1 as well as a-smooth muscle actin and Hoescht staining to quantify pericyte inflammation, myofibroblast conversion and number/viability. This assay is being used to identify novel molecules regulating pericyte function in high content screens.