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

被引:14
作者
Patil, Nandadevi [1 ]
Truong, Vincent [1 ]
Holmberg, Mackenzie H. [2 ,3 ]
Lavoie, Nicolas S. [1 ]
McCoy, Mark R. [2 ]
Dutton, James R. [4 ]
Holmberg, Eric G. [2 ]
Parr, Ann M. [1 ]
机构
[1] Univ Minnesota, Dept Neurosurg, Stem Cell Inst, MMC 96,420 Delaware St SE, Minneapolis, MN 55455 USA
[2] Univ Alaska Anchorage, Dept Chem, Anchorage, AK USA
[3] Univ Washington, Sch Med, Seattle, WA USA
[4] Univ Minnesota, Stem Cell Inst, Dept Genet Cell Biol & Dev, Minneapolis, MN USA
基金
美国国家卫生研究院;
关键词
chronic spinal cord injury; photochemical scar ablation; rose Bengal; FUNCTIONAL REGENERATION; AXONAL REGENERATION; NEUROLOGICAL RECOVERY; ASTROCYTES; GROWTH; INFLAMMATION; HEMISECTION; ORIGIN; INTACT; MODEL;
D O I
10.1089/neu.2017.5398
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
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.
引用
收藏
页码:1745 / 1754
页数:10
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