Deng Li, Lv Jun Qiao, Sun Lin
Third Hospital of Shanxi Medical University, Shanxi Bethune Hospital, Shanxi Academy of Medical Sciences, Tongji Shanxi Hospital, Taiyuan, China.
Front Pharmacol. 2022 Aug 23;13:950368. doi: 10.3389/fphar.2022.950368. eCollection 2022.
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. From a screen of 1,189 papers, which were retrieved from Pubmed, Embase, and Web of science, we identified 28 papers which adhered to strict inclusion and exclusion criteria. Evans blue (EB) leakage on the first day post-SCI was selected as the primary result. Secondary outcomes included the expression of tight junction (TJ) proteins and adhesion junction (AJ) proteins in protein immunoblotting. In addition, we measured functional recovery using the Basso, Beattie, Besnahan (BBB) score and we analyzed the relevant mechanisms to explore the similarities between different studies. The forest plot of Evans blue leakage (EB leakage) reduction rate: the pooled effect size of the 28 studies was 0.54, 95% CI: 0.47-0.61, < 0.01. This indicates that measures to mitigate BSCB damage significantly improved in reducing overall EB leakage. In addition TJ proteins (Occludin, Claudin-5, and ZO-1), AJ proteins (P120 and β-catenin) were significantly upregulated after treatment in all publications. Moreover, BBB scores were significantly improved. Comprehensive studies have shown that 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. In addition, we found that bone marrow mesenchymal stem cell-derived exosomes (BMSC-Exos), which inhibit the TIMP2/MMP signaling pathway, may be the most effective way to alleviate BSCB injury. This study systematically analyzes the experimental treatments and their mechanisms for reducing BSCB injury in the early stage of t-SCI. BMSC-Exos, which inhibit MMP expression, are currently the most effective therapeutic modality for alleviating BSCB damage. In addition, the regulation of MMPs in particular as well as the Akt pathway and the ER stress pathway play important roles in alleviating BSCB injury. https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324794.
创伤性脊髓损伤（t-SCI）是一种严重损伤，对神经功能有毁灭性影响。脊髓损伤后血脊髓屏障（BSCB）的破坏会加重原发性损伤，导致继发性损伤。一系列实验性治疗已被证明可减轻t-SCI后的BSCB破坏。从在PubMed、Embase和Web of science上检索到的1189篇论文中筛选，我们确定了28篇符合严格纳入和排除标准的论文。将SCI后第一天的伊文思蓝（EB）渗漏作为主要结果。次要结果包括蛋白质免疫印迹中紧密连接（TJ）蛋白和黏附连接（AJ）蛋白的表达。此外，我们使用Basso、Beattie、Besnahan（BBB）评分来测量功能恢复情况，并分析相关机制以探索不同研究之间的相似性。伊文思蓝渗漏（EB渗漏）减少率的森林图：28项研究的合并效应大小为0.54，95%CI：0.47 - 0.61，P < 0.01。这表明减轻BSCB损伤的措施在减少总体EB渗漏方面有显著改善。此外，在所有出版物中，治疗后TJ蛋白（闭合蛋白、Claudin-5和ZO-1）、AJ蛋白（P120和β-连环蛋白）均显著上调。而且，BBB评分显著提高。综合研究表明，在t-SCI中，抑制基质金属蛋白酶（MMPs）是减轻BSCB损伤最常用的机制，其次是内质网（ER）应激和Akt途径。此外，我们发现抑制TIMP2/MMP信号通路的骨髓间充质干细胞衍生外泌体（BMSC-Exos）可能是减轻BSCB损伤的最有效方法。本研究系统分析了t-SCI早期减轻BSCB损伤的实验性治疗及其机制。抑制MMP表达的BMSC-Exos目前是减轻BSCB损伤最有效的治疗方式。此外，特别是MMPs的调节以及Akt途径和ER应激途径在减轻BSCB损伤中起重要作用。https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022324794
