Zhang Shuxin, Kluge Bridget, Huang Fengfa, Nordstrom Tuija, Doolen Suzanne, Gross Mica, Sarmiere Patrick, Holmberg Eric G
Spinal Cord Society Research Center, Fort Collins, Colorado 80526, USA.
J Neurotrauma. 2007 Feb;24(2):411-20. doi: 10.1089/neu.2006.0065.
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.
胶质瘢痕是轴突再生的物理和分子屏障,已成为慢性脊髓损伤再生研究的重要靶点。尽管许多方法已被证明在急性损伤模型中对预防瘢痕形成有用,但迄今为止,尚未有描述能有效去除慢性损伤中现有的胶质瘢痕的方法。慢性损伤具有不规则形状的瘢痕,其沿着空洞的整个周边分布。在本研究中,我们将孟加拉玫瑰红(一种常用于生物染色的分子)注射到Long-Evans大鼠脊髓损伤部位的空洞中(25毫米挫伤损伤后5周)。用可见光照射损伤部位。组织学观察表明,至少部分胶质瘢痕组织被孟加拉玫瑰红/光照消融。胶质瘢痕处缺乏胶质纤维酸性蛋白(GFAP)免疫反应性,同时 spared 组织周围的GFAP密度降低,这表明这种光化学瘢痕消融优先杀死瘢痕组织中的星形胶质细胞,但在 spared 组织中的反应程度较小。瘢痕消融后观察到Basso、Beattie和Bresnahan(BBB)量表评分有所降低,但与瘢痕消融治疗前稳定的行为评分相比,差异无统计学意义。我们的研究结果表明,孟加拉玫瑰红/光照对于消融围绕形状不规则的损伤空洞的胶质瘢痕是可行的。当通过细胞或药物治疗富集时,瘢痕消融可能为再生轴突提供一个有利的环境。