Microglia in the Neurovascular Unit: Blood–Brain Barrier–microglia Interactions After Central Nervous System Disorders. (1st May 2019)

• Record Type: Journal Article
• Authors: Thurgur, Hannah; Pinteaux, Emmanuel
• Is Part Of: Neuroscience. Volume 405(2019)
• Page Start: 55
• Page End: 67
• Publication Date: 2019-05-01
• Subjects: AD Alzheimer's disease -- ADAM disintegrin and metalloprotease -- ADEM acute disseminated encephalomyelitis -- AMPK AMP-activated protein kinase -- BBB blood–brain barrier -- CNS central nervous system -- CSF cerebrospinal fluid -- CSF colony-stimulating factor -- CSPGs chondroitin sulfate proteoglycans -- DAMPS danger-associated molecular patterns -- DAP12 DNAX activation protein 12 -- ECM extracellular matrix -- HMGB-1 high-mobility group box -- Iba-1 intracellular calcium-binding protein -- IGF-1 insulin-like growth factor-binding protein -- IL interleukin -- IL-1R1 type 1 IL-1 receptor -- LPS lipopolysaccharides -- MCP-1 monocyte chemoattractant protein-1 -- M-CSF macrophage colony-stimulating factor -- M-CSF-1R macrophage colony-stimulating factor-1 receptor -- MIP-1 macrophage Inflammatory Proteins -- MMPs matrix metalloproteinases -- MS multiple sclerosis -- NMDA N-methyl-D-aspartate -- NVU neurovascular unit -- PD Parkinson's disease -- ROS reactive oxygen species -- TBI traumatic brain injury -- TGF Tmem 119, transmembrane protein 119, transforming growth factor -- TJ tight junctions -- TLR Toll-like receptor -- TNF tumor necrosis factor -- TREM-2 triggering receptor expressed on myeloid cells 2 -- VEGF vascular endothelial growth factor -- ZO Zona Occludens; neurovascular unit -- inflammation -- microglia -- endothelia -- blood–brain barrier; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2018.06.046
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: BBB dysfunction and neuroinflammation are major contributors to CNS disorders. Microglia are key mediators of neuroinflammation. Interpreting microglia–BBB interactions within the context of the NVU provides a more comprehensive overview. This approach will provide novel insights and unravel potential mechanisms of microglia-mediated BBB repair. Abstract: Over the past few decades, microglial cells have been regarded as the main executor of inflammation after acute and chronic central nervous system (CNS) disorders, responding rapidly to exogenous stimuli during acute trauma or infections, or signals released by cells undergoing cell death during conditions such as stroke, Alzheimer's disease (AD) and Parkinson's disease (PD). Barriers of the nervous system, and in particular the blood–brain barrier (BBB), play a key role in the normal physiological and cognitive functions of the brain. Being at the interface between the central and peripheral compartment, the BBB is regarded as a sensor of homeostasis, and any disruption within the brain or the systemic compartment triggers BBB dysfunction and neuroinflammation, both contributing to the pathogenesis of cerebrovascular disease. This involves a dynamic response mediated by all components of the neurovascular unit (NVU), and ongoing research suggests that BBB–microglia interaction is critical to dictate the microglial response to NVU injury. The present review aims to give an up-to-date account of the emerging critical role of BBB–microglia interactions during neuroinflammation, and how these could be targeted for the therapeutic treatment of major central inflammatory disease.