Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis.

Masterman E and Ahmed Z

Cells (2021) 10:

DOI: 10.3390/cells10102682

Abstract

The incidence of spinal cord injury (SCI) is ever-growing, resulting in life-changing neurological deficits which can have devastating long-term impacts on a person’s quality of life. There is an unmet clinical need for a treatment which will prevent progression of the injury, allowing improved axonal regeneration and functional recovery to occur. The initial mechanical insult, followed by a cascade of secondary mechanisms, leads to the exacerbation and remodelling of the lesion site, thus inhibiting neurological recovery. Oedema rapidly accumulates following SCI and contributes to the detrimental pathophysiology and worsens functional outcomes. This study systematically reviewed the current experimental treatments being explored in the field of SCI, which specifically target oedema. Abiding by PRISMA guidelines and strict inclusion criteria, 14 studies were identified and analysed from three online databases (PubMed, Web of Science and EMBASE). As a result, we identified three key modalities which attenuate oedema: selective inhibition of the main water channel protein, aquaporin 4 (AQP4), modulation of inflammation and surgical interventions. Collectively, however, they all result in the downregulation of AQP4, which crucially leads to a reduction in oedema and improved functional outcomes. We concluded that trifluoperazine (TFP), a calmodulin kinase inhibitor which prevents the cell-surface localisation of AQP4, was the most efficacious treatment, significantly eliminating oedema within 7 days of administration. To date, this study is the most concise analysis of current experimental treatments for oedema, exposing its molecular mechanisms and assessing potential therapeutic pathways for future research.

Citation

Masterman E, & Ahmed Z. (2021). Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis. Cells, 10(10). https://doi.org/10.3390/cells10102682 Animals, Rats, Humans, Recovery of Function, Treatment Outcome, Publication Bias, Risk, Spinal Cord, Motor Activity, Spinal Cord Injuries, Blood-Brain Barrier/pathology, Edema/*complications/physiopathology/*therapy, Spinal Cord Injuries/*complications/physiopathology/*therapy

Keywords

• Animals
• Rats
• Humans
• Recovery of Function
• Treatment Outcome
• Publication Bias
• Risk
• Spinal Cord
• Motor Activity
• Spinal Cord Injuries
• Blood-Brain Barrier/pathology
• Edema/*complications/physiopathology/*therapy
• Spinal Cord Injuries/*complications/physiopathology/*therapy