Astrocyte barriers to neurotoxic inflammation

• Published in: Nature reviews. Neuroscience Vol. 16; no. 5; pp. 249 - 263
• Main Author: Sofroniew, Michael V.
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 01.05.2015; Nature Publishing Group
• Subjects: 631/250/256; 631/378/2596/1308; 64/60; 64/86; 692/699/375/534; 82/51; 96/35; 96/44; Animal Genetics and Genomics; Animals; Astrocytes; Astrocytes - metabolism; Behavioral Sciences; Biological Techniques; Biomedicine; Blood vessels; Cell Communication - physiology; Central nervous system diseases; Central Nervous System Diseases - metabolism; Central Nervous System Diseases - pathology; Central Nervous System Diseases - prevention & control; Development and progression; Health aspects; Humans; Immune response; Immune system; Inflammation; Inflammation - metabolism; Inflammation - pathology; Inflammation - prevention & control; Inflammation Mediators - metabolism; Leukocytes; Neurobiology; Neurons - metabolism; Neurons - pathology; Neurosciences; Neurotoxicity; Physiological aspects; review-article; United States > US; California
• ISSN: 1471-003X; 1471-0048; 1469-3178
• DOI: 10.1038/nrn3898

Key Points Astrocytes form borders that separate neural from non-neural tissue along all perivascular spaces, meninges and tissue lesions in the CNS. These borders serve as functional barriers that restrict the entry of inflammatory cells into CNS parenchyma in health and disease. Astrocytes have powerful pro-inflammatory potential and can produce a wide range of molecules that recruit and instruct diverse leukocytes. Transgenic loss-of-function studies, combined with animal models of CNS injury and disease, are revealing that astrocytes have crucial roles in attracting and restricting CNS inflammation. Astrocytes are emerging as pivotal regulators of CNS inflammatory responses, with important implications for diverse CNS disorders. Primary astrocyte dysfunctions are increasingly recognized as having the potential to precipitate, or contribute to, neuronal dysfunctions that underlie neurological symptoms and clinical disorders, leading to the concept of astrocytopathies. Astrocytes form borders that separate neural from non-neural tissue in both normal brain tissue and CNS lesions. In this Review, Michael Sofroniew discusses evidence that astrocytes along such borders have crucial roles in both attracting and restricting CNS inflammation, with important implications for diverse CNS disorders. Astrocytes form borders (glia limitans) that separate neural from non-neural tissue along perivascular spaces, meninges and tissue lesions in the CNS. Transgenic loss-of-function studies reveal that astrocyte borders and scars serve as functional barriers that restrict the entry of inflammatory cells into CNS parenchyma in health and disease. Astrocytes also have powerful pro-inflammatory potential. Thus, astrocytes are emerging as pivotal regulators of CNS inflammatory responses. This Review discusses evidence that astrocytes have crucial roles in attracting and restricting CNS inflammation, with important implications for diverse CNS disorders.