PMID- 25119834 OWN - NLM STAT- MEDLINE DCOM- 20150623 LR - 20240213 IS - 1557-1904 (Electronic) IS - 1557-1890 (Print) IS - 1557-1890 (Linking) VI - 9 IP - 5 DP - 2014 Dec TI - Emerging roles of pericytes in the regulation of the neurovascular unit in health and disease. PG - 591-605 LID - 10.1007/s11481-014-9557-x [doi] AB - Pericytes of the central nervous system (CNS) are uniquely positioned within a multicellular structure termed the neurovascular unit (NVU) to provide crucial support to blood brain barrier (BBB) formation, maintenance, and stability. Numerous CNS diseases are associated with some aspect of BBB dysfunction. A dysfunction can manifest as one or multiple disruptions to any of the following barriers: physical, metabolic, immunological and transport barrier. A breach in the BBB can notably result in BBB hyper-permeability, endothelial activation and enhanced immune-endothelial interaction. How the BBB is regulated within this integrated unit remains largely unknown, especially as it relates to pericyte-endothelial interaction. We summarize the latest findings on pericyte origin, possible marker expression, and availability within different organ systems. We highlight pericyte-endothelial cell interactions, concentrating on extra- and intra- cellular signaling mechanisms linked to platelet derived growth factor-B, transforming growth factor -beta, angiopoietins, Notch, and gap junctions. We discuss the role of pericytes in the NVU under inflammatory insult, focusing on how pericytes may indirectly affect leukocyte CNS infiltration, the direct role of pericyte-mediated basement membrane modifications, and immune responses. We review new findings of pericyte actions in CNS pathologies including Alzheimer's disease, stroke, multiple sclerosis, diabetic retinopathy, and HIV-1 infection. The uncovering of the regulatory role of pericytes on the BBB will provide key insight into how barrier integrity can be re-established during neuroinflammation. FAU - Hill, Jeremy AU - Hill J AD - Department of Pathology and Laboratory Medicine, Temple University School of Medicine, Philadelphia, PA, USA. FAU - Rom, Slava AU - Rom S FAU - Ramirez, Servio H AU - Ramirez SH FAU - Persidsky, Yuri AU - Persidsky Y LA - eng GR - AA015913/AA/NIAAA NIH HHS/United States GR - R01 MH065151/MH/NIMH NIH HHS/United States GR - P30 DA013429/DA/NIDA NIH HHS/United States GR - NS086570/NS/NINDS NIH HHS/United States GR - R37 AA015913/AA/NIAAA NIH HHS/United States GR - R01 AA015913/AA/NIAAA NIH HHS/United States GR - MH65151/MH/NIMH NIH HHS/United States GR - DA013429/DA/NIDA NIH HHS/United States GR - R01 NS086570/NS/NINDS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, Non-U.S. Gov't PT - Review DEP - 20140814 PL - United States TA - J Neuroimmune Pharmacol JT - Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology JID - 101256586 SB - IM MH - Animals MH - Blood-Brain Barrier/cytology/*metabolism/pathology MH - Central Nervous System Diseases/*metabolism/pathology MH - Endothelium, Vascular/cytology/*metabolism MH - *Health Status MH - Humans MH - Pericytes/*physiology MH - Signal Transduction/physiology PMC - PMC4209199 MID - NIHMS621108 COIS- Conflict of Interest The authors of this manuscript declare that there are no actual or potential conflicts of interest EDAT- 2014/08/15 06:00 MHDA- 2015/06/24 06:00 PMCR- 2015/12/01 CRDT- 2014/08/15 06:00 PHST- 2014/06/05 00:00 [received] PHST- 2014/07/10 00:00 [accepted] PHST- 2014/08/15 06:00 [entrez] PHST- 2014/08/15 06:00 [pubmed] PHST- 2015/06/24 06:00 [medline] PHST- 2015/12/01 00:00 [pmc-release] AID - 10.1007/s11481-014-9557-x [doi] PST - ppublish SO - J Neuroimmune Pharmacol. 2014 Dec;9(5):591-605. doi: 10.1007/s11481-014-9557-x. Epub 2014 Aug 14.