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

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 axon...

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Detalles Bibliográficos
Autores principales: Masterman, Emma, Ahmed, Zubair
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534777/
https://www.ncbi.nlm.nih.gov/pubmed/34685662
http://dx.doi.org/10.3390/cells10102682
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author Masterman, Emma
Ahmed, Zubair
author_facet Masterman, Emma
Ahmed, Zubair
author_sort Masterman, Emma
collection PubMed
description 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.
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spelling pubmed-85347772021-10-23 Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis Masterman, Emma Ahmed, Zubair Cells Review 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. MDPI 2021-10-07 /pmc/articles/PMC8534777/ /pubmed/34685662 http://dx.doi.org/10.3390/cells10102682 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Review
Masterman, Emma
Ahmed, Zubair
Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title_full Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title_fullStr Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title_full_unstemmed Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title_short Experimental Treatments for Oedema in Spinal Cord Injury: A Systematic Review and Meta-Analysis
title_sort experimental treatments for oedema in spinal cord injury: a systematic review and meta-analysis
topic Review
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8534777/
https://www.ncbi.nlm.nih.gov/pubmed/34685662
http://dx.doi.org/10.3390/cells10102682
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