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  4. Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation

Different Functions of Recombinantly Expressed Domains of Tenascin-C in Glial Scar Formation

Frontiers in Immunology, 2021 · DOI: 10.3389/fimmu.2020.624612 · Published: February 19, 2021

Spinal Cord InjuryImmunologyNeurology

Simple Explanation

This study investigates the role of different Tenascin-C (TnC) protein fragments in glial scar formation after spinal cord injury (SCI). TnC is a protein that's expressed after injuries in the central nervous system. The researchers used astrocyte cultures from mice with and without TnC to test how different TnC fragments affect gap closure, cell growth, and the expression of certain proteins and cytokines. The study suggests that TnC, particularly the FnD fragment, plays a role in delaying astrocyte reaction and restricting their location to the injury border, allowing microglia/macrophages to form a lesion core during early glial scar formation.

Study Duration
Not specified
Participants
Wild-type C57BL/6 (TnC+/+) mice and constitutively tenascin-C deficient (TnC-/-) mice
Evidence Level
Original Research

Key Findings

  • 1
    TnC fragments delay gap closure in astrocyte cultures, primarily by reducing astrocyte proliferation. The most potent fragments were FnD, FnA, and their combination.
  • 2
    Astrocyte cultures lacking TnC (TnC-/-) showed higher levels of GFAP (a marker for astrocytes) regardless of treatment with TnC fragments.
  • 3
    In vivo, FnD treatment in TnC-/- mice increased the density of activated microglia/macrophages in the injury region, without affecting overall cell proliferation.

Research Summary

This study examined the impact of individual TnC fragments on astrocytic physiology in vitro and in vivo after spinal cord injury (SCI). The results indicated that TnC fragments delay gap closure in vitro in an astrocyte scratch assay, mainly due to decreasing astrocyte proliferation and upregulating mRNA levels of pro-inflammatory cytokines. The findings suggest that TnC, particularly the FnD fragment, mediates the restriction of astrocyte functions to the border of the injury site, allowing microglia/macrophages to form a lesion core during early glial scar formation.

Practical Implications

Therapeutic Target Identification

Modulation of TnC isoforms and their interaction partners could be considered as valuable targets for therapeutic approaches.

Glial Scar Formation

Understanding the role of TnC fragments in glial scar formation can lead to better strategies for promoting regeneration after SCI.

Microglia/Macrophage Activation

Targeting the FnD fragment to control microglia/macrophage activation could improve outcomes after spinal cord injury.

Study Limitations

  • 1
    The mechanical stretching of an astrocyte monolayer is not the most adequate model for assaying glial scar formation since it lacks many components of in vivo injury
  • 2
    Further research is needed to dissect the heterophilic interaction partners which mediate the effects of TnC fragments on astrocytes and microglia/ macrophages upon injury.
  • 3
    The study only evaluates the early phase of inflammation (7 days after injury), and long-term effects of TnC fragments are not examined.

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