Following experimental spinal cord injury (SCI), there is a delayed loss of neurofilament proteins but relatively little is known regarding the status of other cytoskeletal elements. The purpose of the present study was to compare the extent and time course of the MAP2 loss with that of neurofilament proteins, and to examine tau protein levels and distribution following SCI. Within 1 to 6 hours following SCI, there is rapid loss of MAP2, tau, and nonphosphorylated neurofilament proteins at the injury site. In contrast, the loss of phosphorylated neurofilament proteins was not significant until 1 week postinjury. In addition to the loss of MAP2 protein, there was extensive beading of MAP2-immunoreactive dendrites extending into the white matter. This was most pronounced 1 hour after injury and gradually resolved such that beading was no longer evident 2 weeks after SCI. The time course of beading resolution is similar to that of behavioral recovery following SCI, but the functional significance of the beading remains to be determined. Together, these results demonstrate that there are 2 phases of cytoskeletal disruption following SCI; a rapid loss of MAP2, tau, and nonphosphorylated neurofilament proteins, and a delayed loss of phosphorylated neurofilaments.
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.
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