Experimental treatments to attenuate blood spinal cord barrier rupture in rats with traumatic spinal cord injury: A meta-analysis and systematic review

Frontiers in Pharmacology, 2022 · DOI: 10.3389/fphar.2022.950368 · Published: August 23, 2022

Spinal Cord Injury Pharmacology Neurology

Simple Explanation

Traumatic spinal cord injury (t-SCI) is a severe injury that has a devastating impact on neurological function. Blood spinal cord barrier (BSCB) destruction following SCI aggravates the primary injury, resulting in a secondary injury. A series of experimental treatments have been proven to alleviate BSCB destruction after t-SCI. This study systematically analyzes the experimental treatments and their mechanisms for reducing BSCB injury in the early stage of t-SCI. The study found that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), which inhibit MMP expression, are currently the most effective therapeutic modality for alleviating BSCB damage.

Study Duration

Not specified

Participants

Rats

Evidence Level

Systematic Review and Meta-Analysis

Key Findings

1
The pooled effect size of the 28 studies was 0.54, 95% CI: 0.47–0.61, p < 0.01, indicating that measures to mitigate BSCB damage signiﬁcantly improved in reducing overall EB leakage.
2
TJ proteins (Occludin, Claudin-5, and ZO-1), AJ proteins (P120 and β-catenin) were signiﬁcantly upregulated after treatment in all publications.
3
In t-SCI, inhibition of matrix metalloproteinases (MMPs) is the most commonly used mechanism to mitigate BSCB damage, followed by endoplasmic reticulum (ER) stress and the Akt pathway.

Research Summary

This study systematically reviews experimental therapies focused on mitigating BSCB injury after t-SCI over the past 10 years. The study found that BMSC-Exos may be the most effective treatment for reducing BSCB damage by inhibiting the expression and activity of MMPs. Regulation of MMPs, the Akt pathway and ER stress pathway can improve the damage of BSCB in t-SCI and promote recovery of neurological function.

Practical Implications

Drug Development

The data summarized here may be useful in future drug development and clinical translation studies.

Therapeutic Strategies

Combining different mechanisms (inhibiting MMPs, ER Stress, and regulating the Akt pathway) may achieve the best treatment strategies to alleviate BSCB damage.

New Techniques

The application of hydrogels, nanomaterials, and exosomes may generate more signiﬁcant therapeutic effects for BSCB disruption.

Study Limitations

1
The study focused on the first day after injury as the inclusion criterion.
2
The timing of BBB score measurement varies across studies.
3
Medium to high risk of bias in many studies due to the lack of clear reporting of relevant items.

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