Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Nandadevi Patil; Vincent Truong; MacKenzie H. Holmberg; Nicolas S. Lavoie; Mark R. McCoy; James R Dutton; Eric G. Holmberg; Ann M Parr

doi:10.1089/neu.2017.5398

Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Nandadevi Patil, Vincent Truong, MacKenzie H. Holmberg, Nicolas S. Lavoie, Mark R. McCoy, James R Dutton, Eric G. Holmberg, Ann M Parr

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. We have removed existing scar tissue in chronically contused rat spinal cord using a rose Bengal-based photo ablation approach. In this study, we compared two chemically modified rose bengal derivatives to unmodified rose bengal, both confirming and expanding on our previously published report. Rats were treated with unmodified rose bengal (RB1) or rose bengal modified with hydrocarbon (RB2) or polyethylene glycol (RB3), to determine the effects on scar components and spared tissue post-treatment. Our results showed that RB1 was more efficacious than RB2, while still maintaining minimal collateral effects on spared tissue. RB3 was not taken up by the cells, likely because of its size, and therefore had no effect. Treatment with RB1 also resulted in an increase in serotonin eight days post-treatment in chronically injured spinal cords. Thus, we suggest that unmodified rose Bengal is a potent candidate agent for the development of a therapeutic strategy for scar ablation in chronic SCI.

Original language	English (US)
Pages (from-to)	1745-1754
Number of pages	10
Journal	Journal of neurotrauma
Volume	35
Issue number	15
DOIs	https://doi.org/10.1089/neu.2017.5398
State	Published - Aug 1 2018

Bibliographical note

Funding Information:
We thank Drs. Thomas Pengo and Mark Sanders at the University Imaging Center (UIC), University of Minnesota for their extensive help in microscopy imaging and analysis. We would like to thank Dr. Karl Oskar Ekvall, Statistical Consulting Center, University of Minnesota, MN for his help in statistical analysis of the data. Funds for this research project were provided by private philanthropy through the University of Minnesota Foundation (UMF), the State of Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program administered by the Minnesota Office of Higher Education (Award Number 105005), and the National Center for Advancing Translational Sciences of the National Institutes of Health (Award Number UL1TR000114). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

Publisher Copyright:
© 2018, Mary Ann Liebert, Inc.

Keywords

chronic spinal cord injury
photochemical scar ablation
rose Bengal

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10.1089/neu.2017.5398

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6033306

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title = "Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury",

abstract = "There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. We have removed existing scar tissue in chronically contused rat spinal cord using a rose Bengal-based photo ablation approach. In this study, we compared two chemically modified rose bengal derivatives to unmodified rose bengal, both confirming and expanding on our previously published report. Rats were treated with unmodified rose bengal (RB1) or rose bengal modified with hydrocarbon (RB2) or polyethylene glycol (RB3), to determine the effects on scar components and spared tissue post-treatment. Our results showed that RB1 was more efficacious than RB2, while still maintaining minimal collateral effects on spared tissue. RB3 was not taken up by the cells, likely because of its size, and therefore had no effect. Treatment with RB1 also resulted in an increase in serotonin eight days post-treatment in chronically injured spinal cords. Thus, we suggest that unmodified rose Bengal is a potent candidate agent for the development of a therapeutic strategy for scar ablation in chronic SCI.",

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note = "Funding Information: We thank Drs. Thomas Pengo and Mark Sanders at the University Imaging Center (UIC), University of Minnesota for their extensive help in microscopy imaging and analysis. We would like to thank Dr. Karl Oskar Ekvall, Statistical Consulting Center, University of Minnesota, MN for his help in statistical analysis of the data. Funds for this research project were provided by private philanthropy through the University of Minnesota Foundation (UMF), the State of Minnesota Spinal Cord Injury and Traumatic Brain Injury Research Grant Program administered by the Minnesota Office of Higher Education (Award Number 105005), and the National Center for Advancing Translational Sciences of the National Institutes of Health (Award Number UL1TR000114). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Publisher Copyright: {\textcopyright} 2018, Mary Ann Liebert, Inc.",

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N2 - There are no effective therapies available currently to ameliorate loss of function for patients with spinal cord injuries (SCIs). In addition, proposed treatments that demonstrated functional recovery in animal models of acute SCI have failed almost invariably when applied to chronic injury models. Glial scar formation in chronic injury is a likely contributor to limitation on regeneration. We have removed existing scar tissue in chronically contused rat spinal cord using a rose Bengal-based photo ablation approach. In this study, we compared two chemically modified rose bengal derivatives to unmodified rose bengal, both confirming and expanding on our previously published report. Rats were treated with unmodified rose bengal (RB1) or rose bengal modified with hydrocarbon (RB2) or polyethylene glycol (RB3), to determine the effects on scar components and spared tissue post-treatment. Our results showed that RB1 was more efficacious than RB2, while still maintaining minimal collateral effects on spared tissue. RB3 was not taken up by the cells, likely because of its size, and therefore had no effect. Treatment with RB1 also resulted in an increase in serotonin eight days post-treatment in chronically injured spinal cords. Thus, we suggest that unmodified rose Bengal is a potent candidate agent for the development of a therapeutic strategy for scar ablation in chronic SCI.

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Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Abstract

Bibliographical note

Keywords

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Nikon A1R FLIM Confocal Microscope

University Imaging Centers

Cite this

Safety and Efficacy of Rose Bengal Derivatives for Glial Scar Ablation in Chronic Spinal Cord Injury

Abstract

Bibliographical note

Keywords

Access

OpenUrl availability

Other files and links

Fingerprint

Equipment

Nikon A1R FLIM Confocal Microscope

University Imaging Centers

Cite this