The Use of Etanercept in Animal Models of Spinal Cord Injury: A Systematic Review

Introduction: Traumatic spinal cord injury (SCI) is a severely debilitating condition that often results in permanent motor and sensory deficits. Etanercept, an anti-inflammatory biologic, inhibits tumor necrosis factors (TNF) that have been described to be upregulated in the acute phases following SCI, and believed to contribute to several downstream effects throughout the secondary injury cascade. The current review seeks to synthesize and describe the current literature relating to the potential of etanercept in managing SCI.

Methods: The authors performed a systematic review of the literature in accordance with the Preferred Reporting Items for Systematic reviews and Meta-Analyses (PRISMA) 2020 guidelines. Included were studies accessible as of August 18, 2024, that reported on the use of etanercept following SCI. The studies must have investigated SCI in an in vivo mammalian model (e.g., mouse, rat, rabbit) and originally published in English. Pre-print articles, case reports, conference abstracts, and other reviews were excluded. Searched databases included PubMed, Scopus, and Web of Science; search queries included all MeSH entry terms relating to “Etanercept” and “Spinal Cord Injury”.

Results: Initially, 116 records were identified, with 36 duplicates being removed. Upon screening of the remaining 80 records, 64 were removed for not meeting the inclusion criteria. Thus, the full texts of 16 articles were retrieved. Review of these articles revealed that etanercept has been investigated in the treatment of SCI in various animal models, as both monotherapy as well as in combination with other treatment(s). Thus far in our review, the results from fourteen out of sixteen articles have suggested etanercept to exhibit some degree of benefit post-SCI in preclinical studies.

Conclusion : Despite the current understanding of its pathophysiology, no clinically approved treatments for the devastating and often permanent functional deficits resulting from SCI have been identified. As neuroinflammation is described to be among the earliest mediators of SCI pathophysiology, anti-inflammatories have been widely investigated for early SCI management. Preliminary results of our review suggest that etanercept may modulate early facets of the neuroinflammatory cascade following SCI, which may in turn facilitate functional recovery or protect against worsened outcomes. Further research into the potential of etanercept in SCI is warranted.