Cited by 700Neuroinflammation and Neurodegeneration MechanismsNeuroscience and Neuropharmacology ResearchTraumatic Brain Injury and Neurovascular Disturbances

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Astrogliosis

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Sofroniew, Michael V.·2015·Cold Spring Harbor Perspectives in Biology

DOI 10.1101/cshperspect.a020420PMC PMC4315924

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Abstract

In addition to their many functions in the healthy central nervous system (CNS), astrocytes respond to CNS damage and disease through a process called astrogliosis. For many decades, astrogliosis was sparsely studied and enigmatic. This article examines recent evidence supporting a definition of astrogliosis as a spectrum of heterogeneous potential changes in astrocytes that occur in a context-specific manner as determined by diverse signaling events that vary with the nature and severity of different CNS insults. Astrogliosis is associated with essential beneficial functions, but under specific circumstances can lead to harmful effects. Potential dysfunctions of astrocytes and astrogliosis are being identified that can contribute to, or be primary causes of, CNS disorders, leading to the notion of astrocytopathies. A conceptual framework is presented that allows consideration of normally occurring and dysfunctional astrogliosis and their different roles in CNS disorders.

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Li, J., Wang, Y., Yang, Y., Ren, X., Qiang, Y., Zhang, L., Guo, L., & Liu, K. (2024) · Neuroscience Letters · doi:10.1016/j.neulet.2024.137899 · Cited by 7
Genetic Inhibition of sFRP3 Prevents Glial Reactivity in a Mouse Model of Accelerated Aging
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In vivo assessment of neurodegeneration in Spinocerebellar Ataxia type 7
Parker, J. A., Merchant, S. H. I., Attaripour-Isfahani, S., Cho, H. J., McGurrin, P. M., Brooks, B. P., Spada, A. R. L., Hallett, M., Huryn, L. A., & Horovitz, S. G. (2021) · NeuroImage Clinical · doi:10.1016/j.nicl.2021.102561 · Cited by 7
“Astrogliosis is characterized by a proliferation of astrocytes and morphological changes to them, including cellular and cytoskeletal hypertrophy (Sofroniew, 2014).”
Background
Integrated Metabolomics and Lipidomics Reveal High Accumulation of Glycerophospholipids in Human Astrocytes under the Lipotoxic Effect of Palmitic Acid and Tibolone Protection
Cabezas, R., Martín-Jiménez, C., Zuluaga, M., Pinzón, A. M., Barreto, G. E., & González, J. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23052474 · Cited by 8
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Neuroprotective effect of ACTH on collagenase-induced peri-intraventricular hemorrhage in newborn male rats
Martins, C., Neves, L. T., de Oliveira, M. M. B. P., Bagatini, P. B., da Silva, R. B., Mestriner, R. G., Xavier, L. L., & Rasia‐Filho, A. A. (2020) · Scientific Reports · doi:10.1038/s41598-020-74712-7 · Cited by 7
Corrigendum to ‘Multiple sclerosis: New insights and trends’
Koriem, K. M. M. (2017) · Asian Pacific Journal of Tropical Biomedicine · doi:10.1016/j.apjtb.2017.02.001 · Cited by 7
Direct reprogramming of astrocytes to neurons leads to functional recovery after strokePreprint
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Elucidating brain transport pathways and cell type-dependent gene silencing of a durable lipid–siRNA conjugate administered into cerebrospinal fluid
Sorets, A. G., Schwensen, K. R., Francini, N., Kjar, A., Abdulrahman, A. M., Shostak, A., Katdare, K. A., Schoch, K. M., Cowell, R. P., Park, J. C., et al. (2025) · Nucleic Acids Research · doi:10.1093/nar/gkaf600 · Cited by 6
“Astrogliosis is a multi-faceted process through which astrocytes respond to damage or disease and is characterized by elevated GFAP expression, indicative of cytoskeletal hypertrophy [ 40 ].”
Neuroprotective Efficacy of Astragalus mongholicus in Ischemic Stroke: Antioxidant and Anti-Inflammatory Mechanisms
Hong, Y., Ko, G., Jeon, Y.-J., Baek, H., Lee, J., Lee, D., Park, J., Kim, J., & Chang, K. (2025) · Cells · doi:10.3390/cells14020117 · Cited by 6
“Astrocytes, which support central nervous system homeostasis and blood–brain barrier maintenance, also undergo significant changes post-stroke [3].”
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Kopalli, S. R., Behl, T., Baldaniya, L. H., Ballal, S., Joshi, K. K., Arya, R., Chaturvedi, B., Chauhan, A. S., Verma, R. K., Patel, M., et al. (2025) · Progress in Neuro-Psychopharmacology and Biological Psychiatry · doi:10.1016/j.pnpbp.2025.111375 · Cited by 8
Redox modulation of the complement cascade contributes to synapse loss in Alzheimer's disease
Oh, C.-K., Wang, Y., & Lipton, S. A. (2025) · Neurotherapeutics · doi:10.1016/j.neurot.2025.e00707 · Cited by 6
“Astrocytes play a crucial role in propagating the inflammatory response by releasing ROS/RNS and various inflammatory molecules, which can disturb synaptic plasticity [99].”
Deciphering the Structural Biology of GFAP: Connotations of Its Potency in Presaging the Diagnosis for Traumatic Brain Injury and AD
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“…astrogliosis is characterized by astrocyte proliferation, massive hypertrophy, increased GFAP production, overhanging cellular process, scar formation, and interactions with neighboring neuronal and non-neuronal cell types (peri-vascular fibroblasts, fibrocytes, pericytes, and microglia) [33].”
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Regional spinal cord volumes and pain profiles in AQP4-IgG + NMOSD and MOGAD
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Effect of metabolic disorders on reactive gliosis and glial scarring at the early subacute phase of stroke in a mouse model of diabetes and obesity
Clain, J., Couret, D., Bringart, M., Meilhac, O., d’Hellencourt, C. L., & Diotel, N. (2024) · IBRO Neuroscience Reports · doi:10.1016/j.ibneur.2024.12.002 · Cited by 6
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“2,3 This reaction is delineated morphologically as increased branching and hypertrophy of astrocyte bodies, which is best visualized by immunohistochemistry (IHC).”
Background
Resection of Scar Tissue in Rats With Spinal Cord Injury Can Promote the Expression of βⅢ-tubulin in the Injured Area
Liu, B., Liu, G., Li, C., Liu, S., & Sun, D. (2022) · World Neurosurgery · doi:10.1016/j.wneu.2022.10.069 · Cited by 6
Neurotoxic and cytoprotective mechanisms in the ischemic neocortex
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Interferon regulatory factor 7 modulates virus clearance and immune responses to alphavirus encephalomyelitis
Troisi, E. M., Nguyen, B. H., Baxter, V. K., & Griffin, D. E. (2023) · Journal of Virology · doi:10.1128/jvi.00959-23 · Cited by 6
“Astrocyte expression of intermediate filament protein GFAP is increased during activation (6, 31–33), while microglial cells increase expression of Iba-1 (34).”
In Situ Temporospatial Characterization of the Glial Response to Prion Infection
Michael, A. V., Greenlee, J. J., Harm, T. A., Moore, S. J., Zhang, M., Lind, M. S., Greenlee, M. H. W., & Smith, J. D. (2019) · Veterinary Pathology · doi:10.1177/0300985819861708 · Cited by 6
Downregulated Calcium-Binding Protein S100A16 and HSP27 in Placenta-Derived Multipotent Cells Induce Functional Astrocyte Differentiation
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Editorial: Glia in Health and Disease
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“, 2016; Verkhratsky and Parpura, 2016); the latter producing numerous reactive phenotypes with neuroprotective or neurotoxic features (Pekny and Pekna, 2014; Sofroniew, 2014a; Liddelow et al., 2017).”
Background
Plasma GFAP as a mediator and moderator of Aβ, tau, and neurodegeneration in Alzheimer’s disease
Kim, J. S., Yi, D., Byun, M. S., Ahn, H., Jung, G., Choi, H., Lee, J., Kang, K. M., Chul-Ho, S., Lee, Y.-S., et al. (2026) · npj Dementia · doi:10.1038/s44400-025-00051-x · Cited by 5
“Astrogliosis is known to impair metabolic support for neurons, exacerbate excitotoxicity by reducing glutamate uptake,anddisruptsynapticfunctionwithoutcausing immediatestructural consequences 24 – 26 .”
Soluble epoxide hydrolase inhibition reverses cognitive dysfunction in a mouse model of metabolic syndrome by modulating inflammation
Bah, T. M., Davis, C. M., Allen, E. M., Borkar, R. N., Perez, R., Grafe, M. R., Raber, J., Pike, M. M., & Alkayed, N. J. (2024) · Prostaglandins & Other Lipid Mediators · doi:10.1016/j.prostaglandins.2024.106850 · Cited by 6
Agrin-Lrp4 pathway in hippocampal astrocytes restrains development of temporal lobe epilepsy through adenosine signaling
Liu, Z., Li, Y., Wang, D.-L., Wang, Y., Qiu, W.-T., Qiu, Y.-Y., Zhang, H., You, Q.-L., Liu, S.-M., Liang, Q.-N., et al. (2024) · Cell & Bioscience · doi:10.1186/s13578-024-01241-5 · Cited by 5
“For instance, astrogliosis is a hallmark of focal epilepsy [10].”
Background
Potential role of remimazolam in alleviating bone cancer pain in mice via modulation of translocator protein in spinal astrocytes
Peng, Y., Zhang, Y., Wang, W., Liu, B., Zhang, Z., Gong, Z., Zhang, X., Xia, Y., You, X., & Wu, J. (2024) · European Journal of Pharmacology · doi:10.1016/j.ejphar.2024.176861 · Cited by 5
Roles of glia-derived extracellular vesicles in central nervous system diseases: an update
Sun, H., Su, X., Li, S., Mu, D., & Qu, Y. (2021) · Reviews in the Neurosciences · doi:10.1515/revneuro-2020-0144 · Cited by 5
Long-Term Capsaicin Administration Ameliorates the Dysfunction and Astrogliosis of the Brain in Aged Mice with Missing Maxillary Molars
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Sustained PGC-1α2 or PGC-1α3 expression induces astrocyte dysfunction and degeneration
Nunes, M. J., Carvalho, A. N., Sá-Lemos, C., Colaço, M. L., Červenka, I., Ciraci, V., Santos, S. G., Ribeiro, M. M., Castanheira, M., Jannig, P. R., et al. (2023) · European Journal of Cell Biology · doi:10.1016/j.ejcb.2023.151377 · Cited by 6
Sustained Retinal Defocus Increases the Effect of Induced Myopia on the Retinal Astrocyte Template
Lin, C. R., Toychiev, A. H., Ablordeppey, R. K., Srinivas, M., & Benavente-Pérez, A. (2024) · Cells · doi:10.3390/cells13070595 · Cited by 7
Neuroserpin and Extracellular Vesicles in Ischemic Stroke: Partners in Neuroprotection?
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Pattern of Neuronal and Axonal Damage, Glial Response, and Synaptic Changes in Rat Cerebellum within the First Week following Traumatic Brain Injury.
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Digoxin Induces Human Astrocyte Reaction In Vitro
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Astrocyte Receptor Rebirth
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Lipid-siRNA conjugate accesses a perivascular transport mechanism and achieves widespread and durable knockdown in the central nervous system
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“44 Immunohistochemical staining of GFAP 1 month after ICV injection did not show any differences between L2-siRNA groups (NTC, Htt) and vehicle (Fig.”
Astrocytic Kir4.1 ion channel deficit drives persistent inflammatory facial pain in males
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Jarrar, B. M., Almansour, M. I., Al-Doaiss, A. A., Jarrar, Q., Lee, S.-J., & Sewelam, A. (2025) · Human & Experimental Toxicology · doi:10.1177/09603271251390978 · Cited by 4
“53 In addition, Au NPs-treated rats, demonstrated neuronal degeneration con ﬁ rmed by activation and proliferation of astrocytes represented as the concomitant upregulation of GFAP immune-expression.”
Neuroglia in autoimmune encephalitis
Ismail, F. S., Faustmann, P. M., Corvace, F., & Faustmann, T. J. (2025) · Handbook of clinical neurology · doi:10.1016/b978-0-443-19102-2.00002-8 · Cited by 5
Differential Responses of Primary Astrocytes Under Hyperthermic Temperatures
Qiu, J., Jin, G., Huang, G., Huang, H., & Xu, F. (2022) · IEEE Transactions on Biomedical Engineering · doi:10.1109/tbme.2022.3186509 · Cited by 4

Authors: Sofroniew, M. V.
Affiliations: University of California, Los Angeles (US)
Corresponding author: Sofroniew, Michael V.
ORCID: Sofroniew, Michael V.
Venue: Cold Spring Harbor Perspectives in Biology
Publisher: Cold Spring Harbor Laboratory
Published: 2014-11-07
Volume: 7
Issue: 2
Pages: a020420
ISSN: 1943-0264 (ISSN-L)
DOI: 10.1101/cshperspect.a020420
PMC: PMC4315924
OpenAlex: W4239346618
Cited by: 695
References: 109
Citations by year: 2026: 44 · 2025: 53 · 2024: 84 · 2023: 83 · 2022: 101 · 2021: 83 · 2020: 86 · 2019: 61 · 2018: 38 · 2017: 27 · 2016: 21 · 2015: 13 · 2014: 1
Type: posted content
Language: en
Open access: bronze
doi.org
Locations: Cold Spring Harbor Perspectives in Biology (publishedVersion)
Europe PMC (PubMed Central) (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health
Topics: Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
Health Sciences › Medicine › Clinical Neurology › Traumatic Brain Injury and Neurovascular Disturbances
Keywords: astrocyte activation, astrocytes, astrocytopathy, central nervous system injury, central nervous system disorders, astrocyte dysfunction
MeSH terms: Astrocytes, Cell Communication, Cell Movement, Central Nervous System, Central Nervous System Diseases, Cicatrix, Models, Biological, Mutation, Signal Transduction

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