Pathological hemodynamic changes and leukocyte transmigration disrupt the blood–spinal cord barrier after spinal cord injury

Journal of Neuroinflammation, 2023 · DOI: https://doi.org/10.1186/s12974-023-02787-w · Published: May 1, 2023

Simple Explanation

Spinal cord injury (SCI) can lead to long-term disabilities, and secondary injuries worsen the damage. The blood-spinal cord barrier (BSCB) protects the spinal cord by preventing harmful substances from entering, but it can be disrupted after SCI, leading to inflammation and further damage. This study used a mouse model to investigate how BSCB disruption spreads after SCI. The researchers found that the disruption occurs rapidly and is linked to gaps forming in the tight junctions (TJs) that normally seal the barrier. They also found that blood flow changes and the movement of leukocytes (immune cells) contribute to the formation of these gaps. The study suggests that interventions targeting blood flow and leukocyte movement could help protect the BSCB and reduce secondary injury after SCI. However, the tested method of target temperature management (TTM) showed little protective effect on the BSCB in the early stages of SCI.

Study Duration

Not specified

Participants

Adult male mice (23 ± 1 g) at 8–10 weeks

Evidence Level

Level 2: Experimental study using a SCI contusion mouse model

Key Findings

1
BSCB disruption occurs rapidly after SCI and spreads to adjacent spinal segments, with gaps appearing in the tight junctions of small vessels.
2
Pathological hemodynamic changes, specifically increased shear force and transmural pressure, contribute to BSCB disruption.
3
Leukocyte transmigration actively induces gap formation and BSCB disruption in the early phase of SCI.

Research Summary

The study investigates the mechanisms of blood-spinal cord barrier (BSCB) disruption following spinal cord injury (SCI) using a mouse model and in vivo imaging techniques. The findings indicate that BSCB disruption is a secondary event characterized by widespread gap formation in tight junctions, influenced by pathological hemodynamic changes and leukocyte transmigration. The study suggests that targeting pathological hemodynamic changes and leukocyte transmigration could provide new therapeutic strategies for protecting the BSCB in SCI.

Practical Implications

Therapeutic Window

The finding that BSCB disruption is a secondary change suggests a potential therapeutic window for clinical intervention before extensive disruption occurs.

Targeted Therapies

The identification of pathological hemodynamic changes and leukocyte transmigration as key contributors to BSCB disruption highlights these factors as potential targets for new treatment strategies.

Ineffectiveness of TTM

The study's conclusion that target temperature management (TTM) is inadequate to protect the BSCB in early SCI suggests the need to explore alternative or adjunctive therapies.

Study Limitations

1
The study mainly focused on venous vessels due to technical limitations in imaging arterial vessels in vivo.
2
The origin of the pathological hemodynamic changes remains unclear.
3
The study's findings on TTM may not be generalizable to all TTM protocols or clinical settings.

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