Cited by 1,851Nerve injury and regenerationSpinal Cord Injury ResearchNeurogenesis and neuroplasticity mechanisms

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Astrocyte scar formation aids central nervous system axon regeneration

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Anderson, Mark A., Burda, Joshua E., Ren, Yilong, Ao, Yan, O’Shea, Timothy M., Kawaguchi, Riki, Coppola, Giovanni, Khakh, Baljit S., Deming, Timothy J., Sofroniew, Michael V.·2016·Nature

DOI 10.1038/nature17623PMC PMC5243141

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Abstract

Transected axons fail to regrow in the mature central nervous system. Astrocytic scars are widely regarded as causal in this failure. Here, using three genetically targeted loss-of-function manipulations in adult mice, we show that preventing astrocyte scar formation, attenuating scar-forming astrocytes, or ablating chronic astrocytic scars all failed to result in spontaneous regrowth of transected corticospinal, sensory or serotonergic axons through severe spinal cord injury (SCI) lesions. By contrast, sustained local delivery via hydrogel depots of required axon-specific growth factors not present in SCI lesions, plus growth-activating priming injuries, stimulated robust, laminin-dependent sensory axon regrowth past scar-forming astrocytes and inhibitory molecules in SCI lesions. Preventing astrocytic scar formation significantly reduced this stimulated axon regrowth. RNA sequencing revealed that astrocytes and non-astrocyte cells in SCI lesions express multiple axon-growth-supporting molecules. Our findings show that contrary to the prevailing dogma, astrocyte scar formation aids rather than prevents central nervous system axon regeneration.

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Authors: Anderson, M. A., Burda, J. E., Ren, Y., Ao, Y., O’Shea, T. M., Kawaguchi, R., Coppola, G., Khakh, B. S., Deming, T. J., & Sofroniew, M. V.
Affiliations: Tongji University (CN)
University of California, Los Angeles (US)
Corresponding author: Sofroniew, Michael V.
ORCID: Anderson, Mark A.
Burda, Joshua E.
Ren, Yilong
O’Shea, Timothy M.
Kawaguchi, Riki
Coppola, Giovanni
Khakh, Baljit S.
Deming, Timothy J.
Sofroniew, Michael V.
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2016-03-30
Volume: 532
Issue: 7598
Pages: 195-200
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/nature17623
PMC: PMC5243141
OpenAlex: W2335534790
Cited by: 1,851
References: 104
Citations by year: 2026: 116 · 2025: 163 · 2024: 180 · 2023: 159 · 2022: 234 · 2021: 250 · 2020: 224 · 2019: 159 · 2018: 162 · 2017: 136 · 2016: 62
FWCI: 97.34
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
eScholarship (California Digital Library) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion)
Infoscience (Ecole Polytechnique Fédérale de Lausanne) (submittedVersion, cc-by-nc-nd)
Funders: National Institute of Mental Health (R01MH099559, MH104069, MH099559A, DP1MH104069)
National Institute of Neurological Disorders and Stroke (NS084030, NS057624, NS060677, R01NS060677, R01NS057624, P30NS062691, R01NS084030)
Topics: Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
Health Sciences › Medicine › Clinical Neurology › Spinal Cord Injury Research
Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Keywords: axon regeneration, spinal cord injury, central nervous system injury, corticospinal axons, sensory axons, serotonergic axons, hydrogel delivery, laminin, axon growth inhibition, astrocytes
MeSH terms: Animals, Astrocytes, Axons, Central Nervous System, Cicatrix, Female, Models, Biological, Nerve Regeneration, Chondroitin Sulfate Proteoglycans, Spinal Cord Injuries, Reproducibility of Results, Genomics, Mice

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