Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Hassan-Abad Square, Imam Khomeini Ave, 11365-3876, Tehran, Iran.
Student's Scientific Research Center (SSRC), Tehran University of Medical Sciences, Tehran, Iran.
Eur Spine J. 2021 Jun;30(6):1474-1494. doi: 10.1007/s00586-021-06718-2. Epub 2021 Jan 24.
Macrophages play an important role in mediating damage after Spinal cord injury (SCI) by secreting macrophage migration inhibitory factor (MMIF) as a secondary injury mediator. We aimed to systematically review the role of MMIF as a therapeutic target after traumatic SCI.
Our systematic review has been performed according to the PRISMA 2009 Checklist. A systematic search in the scientific databases was carried out for studies published before 20 February 2019 from major databases. Two researchers independently screened titles. The risk of bias of eligible articles was assessed, and data were extracted. Finally, we systematically analyzed and interpreted related data.
785 papers were selected for the title and abstract screening. 12 papers were included for data extraction. Eight animal studies were of high quality and the remaining two were of medium quality. One of the two human studies was of poor quality and the other was of fair quality. MMIF as a pro-inflammatory mediator can cause increased susceptibility to glutamate-related neurotoxicity, increased nitrite production, increased ERK activation, and increased COX2/PGE2 signaling pathway activation and subsequent stimulation of CCL5-related chemotaxis. Two human studies and six animal studies demonstrated that MMIF level increases after SCI. MMIF inhibition might be a potential therapeutic target in SCI by multiple different mechanisms (6/12 studies).
Most animal studies demonstrate significant neurologic improvement after administration of MMIF inhibitors, but these inhibitors have not been studied in humans yet. Further clinical trials are need to further understand MMIF inhibitor utility in acute or chronic SCI.
Diagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.
巨噬细胞通过分泌巨噬细胞迁移抑制因子（MMIF）作为二次损伤介质，在介导脊髓损伤（SCI）后损伤中发挥重要作用。我们旨在系统地综述 MMIF 作为创伤性 SCI 后治疗靶点的作用。
我们根据 PRISMA 2009 清单进行了系统综述。在主要数据库中对 2019 年 2 月 20 日前发表的研究进行了系统搜索。两名研究人员独立筛选标题。评估合格文章的偏倚风险，并提取数据。最后，我们系统地分析和解释了相关数据。
筛选标题和摘要后，共选择了 785 篇论文。纳入了 12 篇论文进行数据提取。8 项动物研究质量较高，其余 2 项质量中等。2 项人类研究中的 1 项质量较差，另 1 项质量一般。作为促炎介质的 MMIF 可导致谷氨酸相关神经毒性易感性增加、亚硝酸盐生成增加、ERK 激活增加、COX2/PGE2 信号通路激活增加以及随后的 CCL5 相关趋化作用刺激增加。2 项人类研究和 6 项动物研究表明，SCI 后 MMIF 水平升高。通过多种不同的机制，MMIF 抑制可能是 SCI 的潜在治疗靶点（12 项研究中的 6 项）。
大多数动物研究表明，给予 MMIF 抑制剂后神经功能显著改善，但这些抑制剂尚未在人类中进行研究。需要进一步的临床试验来进一步了解 MMIF 抑制剂在急性或慢性 SCI 中的应用。
证据等级 I：诊断：具有一致应用的参考标准和盲法的个体横断面研究。
