Neutrophil Extracellular Traps Exacerbate Secondary Injury via Promoting Neuroinﬂammation and Blood–Spinal Cord Barrier Disruption in Spinal Cord Injury

Frontiers in Immunology, 2021 · DOI: 10.3389/fimmu.2021.698249 · Published: August 11, 2021

Simple Explanation

Spinal cord injury (SCI) causes primary damage from the initial trauma, followed by secondary damage from biochemical and cellular processes. Neutrophils, the first inflammatory cells at the injury site, worsen this secondary damage. Neutrophils release neutrophil extracellular traps (NETs), which exacerbate neuroinflammation and disrupt the blood-spinal cord barrier. This leads to increased spinal cord edema and neuronal apoptosis in rats with SCI. Inhibiting NETs formation or disrupting them with DNase 1 reduces secondary damage, limits scar formation, and improves functional recovery after SCI. NETs worsen SCI partly by increasing TRPV4 levels in the injured spinal cord.

Study Duration

Not specified

Participants

198 female Sprague–Dawley (SD) rats

Evidence Level

Level: Not specified, Study type: Animal Study

Key Findings

1
Infiltrated neutrophils produce NETs at the epicenter of the SCI, which contributes to secondary injury.
2
Restricting NETs attenuates neuroinflammation and edema after SCI, reducing cell death and scar formation.
3
NETs promote BSCB disruption, potentially through elevating TRPV4 levels, thus exacerbating secondary injury after SCI.

Research Summary

This study demonstrates that infiltrated neutrophils produce NETs at the injury site, exacerbating secondary injury in SCI by promoting neuroinflammation and disrupting the blood-spinal cord barrier. Inhibition or degradation of NETs reduces cell death, scar formation, and tissue damage, leading to improved motor function recovery, likely through alleviation of neuroinflammation and BSCB disruption. The study identifies TRPV4 as a potential mechanism by which NETs aggravate BSCB disruption, suggesting NETs as a promising therapeutic target for SCI.

Practical Implications

Therapeutic Target

NETs may be a potential therapeutic target for SCI.

Treatment Strategies

Inhibiting NETs formation or degrading NETs could alleviate secondary damage and promote functional recovery after SCI.

Drug Development

Further research into the mechanisms by which NETs exacerbate SCI may lead to the development of novel drugs.

Study Limitations

1
In vitro study is needed to further conﬁrm whether NETs damage endothelial cells through TRPV4 elevation.
2
Whether NETs aggravate SCI through other mechanisms is worth investigating.
3
All these results need to be veriﬁed in various models in the future.

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