Tocilizumab promotes repair of spinal cord injury by facilitating the restoration of tight junctions between vascular endothelial cells

Fluids and Barriers of the CNS, 2023 · DOI: https://doi.org/10.1186/s12987-022-00399-9 · Published: January 1, 2023

Simple Explanation

This study investigates the effect of Tocilizumab, an IL-6 receptor antibody, on the restoration of tight junctions (TJs) between vascular endothelial cells after spinal cord injury (SCI). The study aimed to determine if Tocilizumab could help repair the blood-spinal cord barrier (BSCB) and promote axon regeneration. Mice with SCI were treated with Tocilizumab, and the researchers examined the expression of proteins associated with TJs (CLDN5 and ZO-1) and the leakage of the BSCB. They also assessed axon regeneration and motor function recovery. The results showed that Tocilizumab treatment led to increased expression of TJs proteins, reduced BSCB leakage, decreased inflammation and fibrotic scarring, and improved axon regeneration and motor function recovery, suggesting that Tocilizumab could be a potential therapeutic strategy for SCI.

Study Duration

14 and 28 days postinjury

Participants

78 female C57BL/6J mice

Evidence Level

Not specified

Key Findings

1
Tocilizumab treatment significantly increased the expression of claudin-5 (CLDN5) and zonula occludens-1 (ZO-1) between vascular endothelial cells at 14 and 28 days post-injury.
2
Tocilizumab treatment significantly reduced the leakage of the blood-spinal cord barrier (BSCB) in the injured core after spinal cord injury (SCI).
3
Tocilizumab treatment significantly decreased the infiltration of CD68+ macrophages/microglia and the formation of fibrotic scar in the injured core.

Research Summary

This study demonstrates that Tocilizumab, an IL-6R monoclonal antibody, can effectively reduce the expression of IL-6 in macrophages and facilitate TJs restoration of the BSCB after spinal cord injury (SCI). Tocilizumab treatment promotes the restoration of tight junctions between vascular endothelial cells, reduces BSCB leakage, and inhibits inflammation and fibrotic scarring after SCI. Tocilizumab treatment also facilitates axon regeneration and motor functional recovery in mice after SCI, suggesting it as a potential therapeutic strategy for SCI.

Practical Implications

Potential Therapeutic Strategy

Tocilizumab is identified as a potential therapeutic strategy for spinal cord injury due to its ability to promote BSCB repair and axon regeneration.

Clinical Translation

The findings support the clinical translation of Tocilizumab for SCI treatment, given its existing approval for other conditions.

Targeted Intervention

The study highlights the importance of targeting IL-6 signaling in SCI to promote tissue repair and functional recovery.

Study Limitations

1
The restoration of axons could not reach to normal level by Tocilizumab treatment at 28 dpi.
2
The study used a mouse model, which may not fully represent the complexities of human SCI.
3
The long-term effects of Tocilizumab treatment on SCI recovery were not evaluated.

Your Feedback

Was this summary helpful?

Back to Spinal Cord Injury