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Cited by 84Spinal Cord Injury ResearchNeuroinflammation and Neurodegeneration MechanismsMultiple Sclerosis Research Studies

Activation of Neuroprotective Microglia and Astrocytes at the Lesion Site and in the Adjacent Segments Is Crucial for Spontaneous Locomotor Recovery after Spinal Cord Injury

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Kisucká, Alexandra, Bimbová, Katarína, Bačová, Mária, Gálik, Ján, Lukáčová, Nadežda·2021·Cells
DOI 10.3390/cells10081943PMC PMC8394075
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Abstract

Microglia and astrocytes play an important role in the regulation of immune responses under various pathological conditions. To detect environmental cues associated with the transformation of reactive microglia (M1) and astrocytes (A1) into their polarization states (anti-inflammatory M2 and A2 phenotypes), we studied time-dependent gene expression in naive and injured spinal cord. The relationship between astrocytes and microglia and their polarization states were studied in a rat model after Th9 compression (40 g/15 min) in acute and subacute stages at the lesion site, and both cranially and caudally. The gene expression of microglia/macrophages and M1 microglia was strongly up-regulated at the lesion site and caudally one week after SCI, and attenuated after two weeks post-SCI. GFAP and S100B, and A1 astrocytes were profoundly expressed predominantly two weeks post-SCI at lesion site and cranially. Gene expression of anti-inflammatory M2a microglia (CD206, CHICHI, IL1rn, Arg-1), M2c microglia (TGF-β, SOCS3, IL4R α) and A2 astrocytes (Tgm1, Ptx3, CD109) was greatly activated at the lesion site one week post-SCI. In addition, we observed positive correlation between neurological outcome and expression of M2a, M2c, and A2 markers. Our findings indicate that the first week post-injury is critical for modulation of reactive microglia/astrocytes into their neuroprotective phenotypes.

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  • Cd109 and B3gnt5 are known markers of neuroprotective astrocytes.

    “Notably, Cd109 and B3gnt5 are known markers of neuroprotective astrocytes [27,28]”

    From TREM2-Deficient Microglia Attenuate Tau Spreading In Vivo (2023) · cites this paper as [27]

    Results §3.2 identifies CD109 as a marker of neuroprotective A2 astrocytes. Our copy does not identify B3gnt5 as such a marker; a search for B3gnt5 found no relevant passage. (LLM, conf=0.87)

    Experimental — accuracy not yet measured

  • This astrocyte subcluster was enriched for genes involved in extracellular matrix organization, metabolic support, and inflammatory modulation.

    “This subcluster was enriched for genes involved in extracellular matrix organization [102, 135, 136], metabolic support [135, 137], and inflammatory modulation [138–141].”

    From Tau Ablation Rewires Brain Cell Programs in Health and Restores Function in Disease (2026) · cites this paper as [141]

    The Results (sections 3.1–3.2; page unavailable) report expression of selected reactive and neuroprotective astrocyte markers after spinal cord injury, not enrichment in an astrocyte subcluster. A search for extracellular matrix organization and metabolic support found no passage linking either gene category to a subcluster; the sentence cites other sources for inflammatory modulation. (LLM, conf=0.75)

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Cited by

Sorted by citations

Authors
Kisucká, A., Bimbová, K., Bačová, M., Gálik, J., & Lukáčová, N.
Affiliations
Slovak Academy of Sciences (SK)
Corresponding author
Lukáčová, Nadežda
ORCID
Venue
Cells
Publisher
MDPI AG
Published
2021-07-30
Volume
10
Issue
8
Pages
1943
ISSN
2073-4409 (ISSN-L)
DOI
10.3390/cells10081943
PMC
PMC8394075
OpenAlex
W3189693479
Cited by
84
References
6
Citations by year
2026: 9 · 2025: 14 · 2024: 23 · 2023: 20 · 2022: 16 · 2021: 2
FWCI
10.17
Type
journal article
Language
en
Open access
Licence
Locations
  • Cells (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Topics
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Spinal Cord Injury Research
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
  • Health Sciences › Medicine › Pathology and Forensic Medicine › Multiple Sclerosis Research Studies
Keywords
spinal cord injury, microglial polarization, astrocyte polarization, M2 microglia, A2 astrocytes, M1 microglia, A1 astrocytes, neuroprotection, locomotor recovery, glial fibrillary acidic protein, S100B, CD206, TGF-beta, time-dependent gene expression, lesion site, neurological outcome
MeSH terms
Animals, Astrocytes, Behavior, Animal, Disease Models, Animal, Female, Gene Expression Regulation, Locomotion, Macrophages, Nerve Tissue Proteins, Phenotype, Spinal Cord, Spinal Cord Injuries, Time Factors, Signal Transduction, Rats, Wistar, Microglia, Inflammation Mediators, Recovery of Function, Rats

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