Astrocyte barriers to neurotoxic inflammation
Open accessAbstract
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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Reactive astrogliosis phenomena such as astrocyte proliferation, scar-border formation, and immune-cell recruitment mainly occur when there is disruption of the blood-brain barrier.
“these phenomena mainly occur when there is disruption of the blood–brain barrier (Fig. 1a)7.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [7]
The ‘Astrocyte restriction of CNS inflammation’ section describes proliferation, scar-border formation and inflammatory-cell trafficking at sites of CNS damage. The ‘Astrocyte anti-inflammatory mechanisms’ section links newly proliferated scar-forming astrocytes to blood–brain barrier repair after traumatic injury and describes a mechanism by which astrocytes disrupt the barrier and increase leukocyte extravasation. Neither section establishes that these phenomena mainly occur when the blood–brain barrier is disrupted; page numbers were not available in our copy. (LLM, conf=0.83)
Experimental — accuracy not yet measuredAstrocytes can exacerbate or attenuate inflammation.
“Astrocytes can thus exacerbate or attenuate inflammation [412,413].”
From Revisiting the Pathogenesis of X-Linked Adrenoleukodystrophy (2025) · cites this paper as [412]
A classical gain of beneficial function is the restriction of immune cell infiltration in open injuries by scar-border forming reactive astrocytes.
“Finally, a classical gain of beneficial function is the restriction of immune cell infiltration in open injuries by scar-border forming reactive astrocytes7.”
From Reactive astrocyte nomenclature, definitions, and future directions (2021) · cites this paper as [7]
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- Authors
- Sofroniew, M. V.
- Affiliations
- University of California, Los Angeles (US)
- Corresponding author
- Sofroniew, Michael V.
- Venue
- Nature Reviews Neuroscience
- Published
- 2015-04-20
- Volume
- 16
- Issue
- 5
- Pages
- 249-263
- ISSN
- 1471-003X (ISSN-L)
- 1471-0048
- PMC
- PMC5253239
- OpenAlex
- W2018681635
- Cited by
- 1,202
- References
- 140
- Citations by year
- 2026: 76 · 2025: 114 · 2024: 98 · 2023: 120 · 2022: 103 · 2021: 151 · 2020: 137 · 2019: 126 · 2018: 97 · 2017: 79 · 2016: 72 · 2015: 28
- FWCI
- 7.34
- Type
- journal article
- Language
- en
- Update notices
- erratum (2015-05-08)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Nature reviews. Neuroscience (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- Funders
- Dr. Miriam and Sheldon G. Adelson Medical Research Foundation
- National Institute of Neurological Disorders and Stroke (NS084030, NS057624, R01NS057624, R01NS084030)
- Topics
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
- Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
- Keywords
- astrocytes, glia limitans, neuroinflammation, scar formation, meninges, perivascular spaces, pro-inflammatory signaling, central nervous system lesions, neurodegenerative diseases
- MeSH terms
- Animals, Astrocytes, Cell Communication, Central Nervous System Diseases, Humans, Inflammation, Neurons, Inflammation Mediators
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