Woerly Stéphane, Doan Van Diep, Sosa Norma, de Vellis Jean, Espinosa-Jeffrey Araceli
Organogel Canada Ltée, Sainte-Foy, Québec, Canada.
Mental Retardation Research Center, Neuropsychiatric Institute, David Geffen School of Medicine at UCLA, Los Angeles, California.
J Neurosci Res. 2004 Jan 15;75(2):262-272. doi: 10.1002/jnr.10774.
Spinal cords of adult cats were transected and subsequently reconnected with the biocompatible porous poly (N-[2-hydroxypropyl] methacrylamide) hydrogel, NeuroGel. Tissue repair was examined at various time points from 6-21 months post reconstructive surgery. We examined two typical phenomena, astrogliosis and scar formation, in spines reconstructed with the gel and compared them to those from transected non-reconstructed spines. Confocal examination with double immunostaining for glial fibrillary acidic protein (GFAP) and myelin basic protein (MBP) showed that the interface formed between the hydrogel and the spine stumps did prevent scar formation and only a moderate gliosis was observed. The gel implant provided an adequate environment for growth of myelinated fibers and we saw angiogenesis within the gel. Electron microscopy showed that regenerating axons were myelinated by Schwann cells rather than oligodendrocytes. Moreover, the presence of the gel implant lead to a considerable reduction in damage to distal caudal portions of the spine as assessed by the presence of more intact myelinated fibers and a reduction of myelin degradation. Neurologic assessments of hindlimb movement at various times confirmed that spinal cord reconstruction was not only structural but also functional. We conclude that NeuroGel lead to functional recovery by providing a favorable substrate for regeneration of transected spinal cord, reducing glial scar formation and allowing angiogenesis.
成年猫的脊髓被横断，随后与生物相容性多孔聚（N-[2-羟丙基]甲基丙烯酰胺）水凝胶NeuroGel重新连接。在重建手术后6至21个月的不同时间点检查组织修复情况。我们在使用该凝胶重建的脊髓中研究了两种典型现象，即星形胶质细胞增生和瘢痕形成，并将其与横断未重建脊髓的情况进行比较。用胶质纤维酸性蛋白（GFAP）和髓鞘碱性蛋白（MBP）进行双重免疫染色的共聚焦检查表明，水凝胶与脊髓残端之间形成的界面确实能防止瘢痕形成，仅观察到中度的星形胶质细胞增生。凝胶植入物为有髓纤维的生长提供了适宜的环境，并且我们在凝胶内观察到了血管生成。电子显微镜显示，再生轴突由施万细胞而非少突胶质细胞髓鞘化。此外，通过存在更多完整的有髓纤维以及髓鞘降解的减少来评估，凝胶植入物的存在导致脊髓远端尾部损伤的显著减少。在不同时间对后肢运动进行的神经学评估证实，脊髓重建不仅具有结构性，而且具有功能性。我们得出结论，NeuroGel通过为横断脊髓的再生提供有利的底物、减少胶质瘢痕形成并允许血管生成，从而导致功能恢复。
