Photochemical Scar Ablation in Chronically Contused Spinal Cord of Rat

Abstract

Glial scar represents a physical and molecular barrier to axonal regeneration and has become an important target for regeneration research in chronic spinal cord injury. Although many methods have been proven useful for the prevention of scar formation in an acute injury model, to date no effective method has been described to remove an existing glial scar in a chronic injury. The chronic lesion possesses an irregular shaped scar that lines the entire perimeter of the cavity. In the present study, we used rose bengal, a molecule commonly used for biological staining, injected into the cavity at the injury site of Long-Evans rat spinal cord (5 weeks after 25-mm contusion injury). Visible light was used to illuminate the injury site. Histological observation illustrates that at least partial glial scar tissue is ablated by rose bengal/illumination. The lack of glial fibrillary acidic protein (GFAP) immunoreactivity at the glial scar coupled with the reduction of GFAP density surrounding spared tissue suggests that this photochemical scar ablation preferentially kills astrocytes at the scar tissue but also reacts, to a lesser degree, in the spared tissue. There is an observed reduction of Basso, Beattie, and Bresnahan (BBB) scale scores after scar ablation, but it is not statistically significant from stabilized behavioral scoring prior to the scar ablation treatment. Our findings indicate that the rose bengal/illumination is feasible for ablation of the glial scar which surrounds an irregular lesion cavity in shape. The scar ablation might provide a permissive environment for the regenerating axons when enriched by cellular or drug therapy.

The glial scar in spinal cord injury and repair

“…F., we found that triptolide reduces glial scar formation by inactivating the JAK2-STAT3 signal pathway [134] . Moreover, observations from sporadic studies suggest that compounds such as rolipram [135] , rose Bengal [136] and 7 beta-oH cholesteryloleate [137] may be beneficial in treating SCI by manipulating glial scarring.…”

Modulation of musculoskeletal hyperalgesia by brown adipose tissue activity in mice

“…To determine whether activation of brown adipose tissue is necessary for the transient musculoskeletal hyperalgesia observed after a forced swim, interscapular brown adipose of 12 mice was partially ablated using injection of Rose Bengal, as described in methods [22; 55]. Two weeks later, when exposed to the forced swim, sham-operated mice whose interscapular brown adipose was not ablated exhibited greater decreases in grip force responses immediately after the swim than previously ablated mice (Figure 1).…”

“…To determine whether activation of brown adipose tissue is necessary for the persistent musculoskeletal hyperalgesia observed after a forced swim, the brown adipose of 12 mice was partially ablated using Rose Bengal, as described in methods [22; 55]. Two weeks later, baseline grip force values were unaffected by prior ablation when compared with sham-ablated mice (Figure 5A).…”

“…The area of the interscapular brown adipose tissue was exposed, isolated and exposed to an intense light source for 10 min using a Fiber Optic Illuminator from Cole-Parmer (Vernon Hills, IL). The high intensity lamp (150 watt quartz halogen lamp with fiber optic diameter of 0.3 mm and light intensity set at 50%) is reported to induce the generation of Rose Bengal free radicals that cause a local degeneration of tissue resulting in a partial ablation of the illuminated tissue [22; 55]. To induce similar conditions but without tissue ablation, sham mice were injected with dye and the brown adipose tissue isolated surgically, but not exposed to the high intensity illumination.…”

Scar-modulating treatments for central nervous system injury

“…As a result, it is difficult to ablate this tissue by surgery or laser radiation. Interestingly, after injecting rose Bengal, a biological stain, into the cavity at the injury site in rat spinal cord, researchers found that the glial scar tissue is at least partially ablated by illumination [156] .…”