• Seyed Mohammad Piri, Zahra Ghodsi, Sina Shool, Ali Anjomshoa, Amir Azarhomayoun, Ehsan Jangholi, Hamid Reza Dehghan, Rasha Atlasi, Alexander R Vaccaro, and Vafa Rahimi-Movaghar.
• Sina Trauma and Surgery Research Center, Sina Hospital, Tehran University of Medical Sciences, Hassan-Abad Square, Imam Khomeini Ave, 11365-3876, Tehran, Iran.
• Eur Spine J. 2021 Jun 1; 30 (6): 1474-1494.

PurposeMacrophages 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.MethodsOur 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.Results785 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).ConclusionMost 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.Level Of Evidence IDiagnostic: individual cross-sectional studies with the consistently applied reference standard and blinding.© 2021. The Author(s), under exclusive licence to Springer-Verlag GmbH, DE part of Springer Nature.

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