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.

Dissecting the Dual Role of the Glial Scar and Scar-Forming Astrocytes in Spinal Cord Injury

“…This inference is consistent with the results of Anderson et al (2016). Interestingly, many studies indicate that the removal of chronic scar tissue improves axonal regeneration (Li et al, 2018;Patil et al, 2018;Wang N. et al, 2018). However, the scar tissue removed in these studies includes both the glial scar and the fibrotic scar.…”

Amantadine prevented hypersensitivity and decreased oxidative stress by NMDA receptor antagonism after spinal cord injury in rats

“…In this same sense, positive effects have been observed from pre‐ and post‐treatment with amantadine in models of cortical impact injury (Okigbo et al., 2019) and models of Parkinson's disease induced by 6‐hydroxydopamine (6‐OHDA) (Chattopadhyaya et al., 2015) and by MPP + (Ossola et al., 2011). Based on the evidence presented here, Amantadine may be used also in non‐traumatic SCI, such as neoplasms, vascular disease, inflammatory disease and spinal stenosis (Ho et al., 2007), or even to prevent damage after chemically induced Rose Bengal lesions, due to exacerbated oxidative stress (Patil et al., 2018).…”

Strategies for Oligodendrocyte and Myelin Repair in Traumatic CNS Injury

“…On the other hand, CSPGs that stimulate axon growth and survival have also been identified in the glial scar, lending to arguments of its multifaceted function (Nichol et al, 1994 ; Nakanishi et al, 2006 ; Schäfer and Tegeder, 2018 ). This is further complicated by studies showing little to no effect of glial scar ablation on regeneration (Anderson et al, 2016 ; Patil et al, 2018 ; Haindl et al, 2019 ). Together, the current literature suggests that the glial scar initially serves to prevent healthy axons from entering a region of inflammation and necrosis.…”