Cited by 1,116Traumatic Brain Injury and Neurovascular DisturbancesNeuroinflammation and Neurodegeneration MechanismsSpinal Cord Injury Research

Leukocyte Infiltration, Neuronal Degeneration, and Neurite Outgrowth after Ablation of Scar-Forming, Reactive Astrocytes in Adult Transgenic Mice

Open access
Bush, Toby G, Puvanachandra, Narman, Horner, Catherine H, Polito, Anabella, Ostenfeld, Thor, Svendsen, Clive N, Mucke, Lennart, Johnson, Martin H +1 more·1999·Neuron

Abstract

Reactive astrocytes adjacent to a forebrain stab injury were selectively ablated in adult mice expressing HSV-TK from the Gfap promoter by treatment with ganciclovir. Injured tissue that was depleted of GFAP-positive astrocytes exhibited (1) a prolonged 25-fold increase in infiltration of CD45-positive leukocytes, including ultrastructurally identified monocytes, macrophages, neutrophils, and lymphocytes, (2) failure of blood-brain barrier (BBB) repair, (3) substantial neuronal degeneration that could be attenuated by chronic glutamate receptor blockade, and (4) a pronounced increase in local neurite outgrowth. These findings show that genetic targeting can be used to ablate scar-forming astrocytes and demonstrate roles for astrocytes in regulating leukocyte trafficking, repairing the BBB, protecting neurons, and restricting nerve fiber growth after injury in the adult central nervous system.

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Crossref · 10.1016/s0896-6273(00)80781-3

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1 of 1 references verified0 citation errors · 0 not checkable

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  • Reactive astrocytes induced by ischemia promote CNS recovery and repair.

    “previous studies have provided evidence that reactive astrocytes induced by ischemia promote CNS recovery and repair1,10,11.”

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Authors
Bush, T. G., Puvanachandra, N., Horner, C. H., Polito, A., Ostenfeld, T., Svendsen, C. N., Mucke, L., Johnson, M. H., & Sofroniew, M. V.
Affiliations
  • University of Cambridge (GB)
  • University of California, San Francisco (US)
Corresponding author
Sofroniew, Michael V
Venue
Neuron
Publisher
Elsevier BV
Published
1999-06
Volume
23
Issue
2
Pages
297-308
ISSN
0896-6273 (ISSN-L)
OpenAlex
W1969619562
Cited by
1,116
References
1
Citations by year
2026: 17 · 2025: 31 · 2024: 47 · 2023: 44 · 2022: 48 · 2021: 46 · 2020: 62 · 2019: 47 · 2018: 63 · 2017: 49 · 2016: 58 · 2015: 67 · 2014: 65 · 2013: 53 · 2012: 59
FWCI
12.28
Type
journal article
Language
en
Open access
Locations
  • Neuron (publishedVersion)
  • PubMed (publishedVersion)
Funders
Wellcome Trust
Topics
  • Health Sciences › Medicine › Neurology › Traumatic Brain Injury and Neurovascular Disturbances
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
Keywords
reactive astrocytes, scar formation, leukocyte infiltration, blood-brain barrier repair, neurodegeneration, neurite outgrowth, glutamate receptor blockade, GFAP promoter, stab wounds, monocytes, macrophages, neutrophils, lymphocytes
MeSH terms
Animals, Astrocytes, Blood-Brain Barrier, Brain Injuries, Cell Count, Cell Movement, Female, Gene Expression Regulation, Glial Fibrillary Acidic Protein, Hippocampus, Histocytochemistry, Leukocytes, Mice, Transgenic, Nerve Degeneration, Neurons, Thymidine Kinase, Wounds, Stab, Ganciclovir, Neurites, Simplexvirus, Mice

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