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Astrocyte barriers to neurotoxic inflammation

An Erratum to this article was published on 08 May 2015

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.

Abstract

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.

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Figure 1: Astrocytes form borders (glia limitans) that serve as functional barriers at interfaces between non-neural tissue and CNS neural parenchyma along blood vessels, meninges and tissue lesions.
Figure 2: Dysfunction of astrocyte functional barriers lining inflamed non-neural tissue leads to increased spread of neurotoxic inflammation into adjacent neural parenchyma.
Figure 3: Pro-inflammatory and anti-inflammatory molecular mechanisms of astrocyte borders and functional barriers.
Figure 4: Model of neuromyelitis optica as an astrocytopathy with causal contributions of astrocyte gains and losses of functions at different stages of disease progression.

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Acknowledgements

Work in the author's laboratory is supported by the US National Institutes of Health (grants NS057624 and NS084030), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation, the Hilton Foundation and Wings for Life.

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Correspondence to Michael V. Sofroniew.

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Innate immune responses

Inherent and automatic immune and inflammatory responses to specific molecular cues that do not require previous exposure.

Adaptive immune responses

Acquired immune responses (for example, antibody formation) resulting from prior exposure to molecular cues (antigens) recognized by the host immune system as foreign.

Diapedesis

The passage of blood cells through the intact walls of blood vessels.

Perivascular spaces

Spaces immediately adjacent to the external surface of blood vessels.

Extravasation

The passage of blood or any of its components, such as cells, molecules or fluids, from blood vessels (intact or damaged) into surrounding tissues.

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Sofroniew, M. Astrocyte barriers to neurotoxic inflammation. Nat Rev Neurosci 16, 249–263 (2015). https://doi.org/10.1038/nrn3898

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