The role of pericytes in brain disorders: from the periphery to the brain

It is becoming increasingly apparent that disorders of the brain microvasculature contribute to many neurological disorders. In recent years it has become clear that a major player in these events is the capillary pericyte which, in the brain, is now known to control the blood-brain barrier, regulate blood flow, influence immune cell entry and be crucial for angiogenesis. In this review we consider the under-explored possibility that peripheral diseases which affect the microvasculature, such as hypertension, kidney disease and diabetes, produce central nervous system (CNS) dysfunction by mechanisms affecting capillary pericytes within the CNS. We highlight how cellular messengers produced peripherally can act via signalling pathways within CNS pericytes to reshape blood vessels, restrict blood flow or compromise blood-brain barrier function, thus causing neuronal dysfunction. Increased understanding of how renin-angiotensin, Rho-kinase and PDGFRβ signalling affect CNS pericytes may suggest novel therapeutic approaches to reducing the CNS effects of peripheral disorders.