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Cited by 2,594Neuroinflammation and Neurodegeneration MechanismsSpinal Cord Injury ResearchNeuroscience and Neuropharmacology Research

Molecular dissection of reactive astrogliosis and glial scar formation

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Sofroniew, Michael V.·2009·Trends in Neurosciences
DOI 10.1016/j.tins.2009.08.002PMC PMC2787735
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Abstract

Reactive astrogliosis, whereby astrocytes undergo varying molecular and morphological changes, is a ubiquitous but poorly understood hallmark of all central nervous system pathologies. Genetic tools are now enabling the molecular dissection of the functions and mechanisms of reactive astrogliosis in vivo. Recent studies provide compelling evidence that reactive astrogliosis can exert both beneficial and detrimental effects in a context-dependent manner determined by specific molecular signaling cascades. Reactive astrocytes can have both loss of normal functions and gain of abnormal effects that could feature prominently in a variety of disease processes. This article reviews developments in the signaling mechanisms that regulate specific aspects of reactive astrogliosis and highlights the potential to identify novel therapeutic molecular targets for diverse neurological disorders.

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Crossref · 10.1016/j.tins.2009.08.002

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  • The neuroprotective phenotype of astrocytes promotes neuronal survival and homeostasis, as these astrocytes secrete neurotrophic factors and anti-inflammatory cytokines.

    “Conversely, the “neuroprotective” phenotype of astrocytes promotes neuronal survival and homeostasis, as these astrocytes secrete neurotrophic factors and anti-inflammatory cytokines [184, 187, 188].”

    From Microglial function, INPP5D/SHIP1 signaling, and NLRP3 inflammasome activation: implications for Alzheimer’s disease (2023) · cites this paper as [188]

    The “Reactive astrogliosis and neural protection and repair” section says reactive astrocytes can protect CNS cells, limit neuronal loss, and help stabilize extracellular fluid and ion balance. The “regulation of inflammation” section describes both pro- and anti-inflammatory effects. Neither section identifies secretion of neurotrophic factors and anti-inflammatory cytokines as the mechanism claimed; no page numbers are provided in our copy. (LLM, conf=0.86)

    Experimental — accuracy not yet measured

  • Lipid droplet accumulation and upregulation of key transcripts also occur in reactive astrocytes.

    “Historically, astrocyte activation has been characterized by cellular hypertrophy and an increase in glial fibrillary acidic protein (GFAP) expression; however, recent work has shown that lipid droplet accumulation and the upregulation of key transcripts also occur in reactive astrocytes (Pekny and Nilsson, 2005; Sofroniew, 2009).”

    From Sterol dysregulation in Smith–Lemli–Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk (2022) · cites this paper as Sofroniew, 2009

    The Introduction and “Extensive molecular repertoire of reactive astrocytes” sections describe changes in molecular expression as astrocytes become reactive, supporting the transcript-expression part in broad terms. Our copy does not report lipid droplet accumulation in reactive astrocytes (searched for lipid droplets and lipid accumulation). (LLM, conf=0.84)

    Experimental — accuracy not yet measured

  • Astrocyte activation is characterized by cellular hypertrophy and increased GFAP expression.

    “Historically, astrocyte activation has been characterized by cellular hypertrophy and an increase in glial fibrillary acidic protein (GFAP) expression; however, recent work has shown that lipid droplet accumulation and the upregulation of key transcripts also occur in reactive astrocytes (Pekny and Nilsson, 2005; Sofroniew, 2009).”

    From Sterol dysregulation in Smith–Lemli–Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk (2022) · cites this paper as Sofroniew, 2009

    The 'Defining reactive astrogliosis' section describes progressive cellular hypertrophy and changes in molecular expression in reactive astrocytes. It does not identify increased GFAP expression as one of those changes, so the GFAP-specific part of the claim is not supported by the passages found in our copy. Page numbers were not available. (LLM, conf=0.83)

    Experimental — accuracy not yet measured

  • Astrocyte reactivity is tightly linked to endothelial, which are in turn associated with loss of vascular structural integrity and opening of the BBB.

    “Astrocyte reactivity is tightly linked to endothelial [50], which are in turn associated with loss of vascular structural integrity and opening of the BBB [15, 28, 38, 45, 107, 109, 121].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [109]

    The section on ablation of scar-forming astrocytes reports that removing reactive astrocytes prevented blood–brain barrier repair, supporting a relationship between astrocyte reactivity and vascular-barrier function. Our copy does not establish the more specific claim that astrocyte reactivity is tightly linked to endothelial cells. The later claim about loss of vascular integrity has separate citations and is not attributed to this source. (LLM, conf=0.74)

    Experimental — accuracy not yet measured

  • Hypertrophied astrocytes display thicker intermediate filament bundles, highly upregulate GFAP and are associated with neuroprotection and postlesion regeneration.

    “hypertrophied astrocytes display thicker intermediate filament bundles, highly upregulate GFAP [45, 109] and are associated with neuroprotection and postlesion regeneration [28, 45, 46, 47].”

    From Gliovascular alterations in sporadic and familial Alzheimer's disease: <scp><i>APOE3</i></scp> Christchurch homozygote glioprotection (2023) · cites this paper as [109]

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Authors
Sofroniew, M. V.
Affiliations
University of California, Los Angeles (US)
Corresponding author
Sofroniew, Michael V.
ORCID
Sofroniew, Michael V.
Venue
Trends in Neurosciences
Publisher
Elsevier BV
Published
2009-12
Volume
32
Issue
12
Pages
638-647
ISSN
0166-2236 (ISSN-L)
DOI
10.1016/j.tins.2009.08.002
PMC
PMC2787735
OpenAlex
W2085424855
Cited by
2,594
References
7
Citations by year
2026: 99 · 2025: 128 · 2024: 152 · 2023: 140 · 2022: 171 · 2021: 207 · 2020: 188 · 2019: 177 · 2018: 163 · 2017: 170 · 2016: 183 · 2015: 161 · 2014: 185 · 2013: 167 · 2012: 142
FWCI
7.86
Type
journal article
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Trends in Neurosciences (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of Neurological Disorders and Stroke (NS057624, R21NS042693, R01NS047386, R01NS057624, R21NS042039)
Topics
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Keywords
reactive astrogliosis, glial scar formation, astrocytes, astrocyte dysfunction, neurological disorders
MeSH terms
Animals, Astrocytes, Cicatrix, Gliosis, Humans, Models, Biological, Neurons, Signal Transduction, Drug Delivery Systems, Neuroprotective Agents

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