Brain pericytes acquire a microglial phenotype after stroke

• Published in: Acta neuropathologica Vol. 128; no. 3; pp. 381 - 396
• Main Authors: Özen, Ilknur, Deierborg, Tomas, Miharada, Kenichi, Padel, Thomas, Englund, Elisabet, Genové, Guillem, Paul, Gesine
• Format: Journal Article
• Language: English
• Published: Berlin/Heidelberg Springer Berlin Heidelberg 01.09.2014; Springer; Springer Nature B.V
• Subjects: Angiogenesis; Animals; Antigens, CD - metabolism; Arabidopsis Proteins - metabolism; Basic Medicine; Blood vessels; Blood-brain barrier; Brain; Brain - pathology; Calcium-Binding Proteins - metabolism; Case-Control Studies; Cells, Cultured; Disease Models, Animal; Gene Expression Regulation - genetics; Genetic aspects; Genotype & phenotype; Glucose - deficiency; Humans; Hypoxia; Injuries; Intramolecular Transferases - metabolism; Investigations; Ischemia; Ki-67 Antigen - metabolism; Laboratory animals; Medical and Health Sciences; Medicin och hälsovetenskap; Medicine; Medicine & Public Health; Medicinska och farmaceutiska grundvetenskaper; Mice; Mice, Transgenic; Microfilament Proteins - metabolism; Microglia - metabolism; Microglia - pathology; Nerve Tissue Proteins - metabolism; Neuropathology; Neurosciences; Neurovetenskaper; Original Paper; Pathology; Pericytes - pathology; Proteins; RGS Proteins - genetics; RGS Proteins - metabolism; Stroke; Stroke - pathology; Time Factors; Traumatic brain injury; Sweden; Pericytes; Human brain; Stroke; Microglia; Regulator of G-protein signaling 5
• ISSN: 0001-6322; 1432-0533; 1432-0533
• DOI: 10.1007/s00401-014-1295-x

Pericytes are located on the abluminal side of endothelial cells lining the microvasculature in all organs. They have been identified as multipotent progenitor cells in several tissues of the body including the human brain. New evidence suggests that pericytes contribute to tissue repair, but their role in the injured brain is largely unknown. Here, we investigate the role of pericytes in ischemic stroke. Using a pericyte-reporter mouse model, we provide unique evidence that regulator of G-protein signaling 5 expressing cells are activated pericytes that leave the blood vessel wall, proliferate and give rise to microglial cells after ischemic brain injury. Consistently, we show that activated pericytes express microglial markers in human stroke brain tissue. We demonstrate that human brain-derived pericytes adopt a microglial phenotype and upregulate mRNA specific for activated microglial cells under hypoxic conditions in vitro. Our study indicates that the vasculature is a novel source of inflammatory cells with a microglial phenotype in brain ischemia and hence identifies pericytes as an important new target for the development of future stroke therapies.