Stichel C C, Lips K, Wunderlich G, Müller H W
Molecular Neurobiology Laboratory, Department of Neurology, University of Düsseldorf, Germany.
Exp Neurol. 1996 Jul;140(1):21-36. doi: 10.1006/exnr.1996.0111.
Schwann cell (SC) transplantation has emerged as a powerful tool to promote regeneration in the lesioned central nervous system (CNS). Most studies focused on the use of guidance channels to introduce the SCs into CNS neuropil; a technique that itself causes extensive damage to host tissue and is only applicable in superficial brain areas. The present study examines the efficacy of microinjected SC suspensions to promote structural reconstruction of the transected postcommissural fornix in the adult rat. Stereotactic, unilateral fornix transection was performed using a tungsten wire knife. Immediately after transection lesion cavities received either a Dulbecco's modified Eagle's medium injection or a pure SC suspension graft derived from a highly purified SC culture that was prepared from syngeneic rat (P1) sciatic nerves. After 4 days to 8 months, the implant characteristics as well as the structural reconstruction of the tract were analyzed using immunocytochemical methods and anterograde tracing techniques. Numerous SCs of the graft could be identified for up to 8 months. They rapidly dispersed from the injection site and migrated freely for considerable distances into the host tissue. The SCs exhibited a low proliferation activity that ceased within 2 weeks after transplantation. They did not prevent retrograde axonal degeneration of the fornix tract for a short distance (600 micron) but promoted structural reconstruction of the transected fornix tract. Regenerating fibers traversed the lesion site and extended along their former pathway up to the mammillary body, their proper target. Moreover, the applied transplantation technique allowed remyelination of the regenerating fibers by host oligodendrocytes. In conclusion, microtransplantation of SC suspensions represents a promising strategy for promoting structural reconstruction of lesioned CNS projections.
雪旺细胞(SC)移植已成为促进受损中枢神经系统(CNS)再生的有力工具。大多数研究集中于使用引导通道将雪旺细胞引入中枢神经系统神经纤维网;该技术本身会对宿主组织造成广泛损伤,且仅适用于脑浅表区域。本研究检测了显微注射雪旺细胞悬液促进成年大鼠连合后穹窿横断后结构重建的效果。使用钨丝刀进行立体定向单侧穹窿横断。横断后立即向损伤腔注射杜氏改良伊格尔培养基或注射源自同基因大鼠(P1)坐骨神经高度纯化雪旺细胞培养物的纯雪旺细胞悬液移植物。4天至8个月后,使用免疫细胞化学方法和顺行示踪技术分析移植物特征以及神经束的结构重建情况。在长达8个月的时间里都能识别出移植物中的大量雪旺细胞。它们迅速从注射部位散开,并自由迁移相当长的距离进入宿主组织。雪旺细胞增殖活性较低,移植后2周内停止。它们在短距离(600微米)内并不能阻止穹窿束的逆行性轴突退变,但能促进横断穹窿束的结构重建。再生纤维穿过损伤部位,并沿其先前路径延伸至其正确靶点乳头体。此外,所应用的移植技术使宿主少突胶质细胞能够对再生纤维进行髓鞘化。总之,雪旺细胞悬液的微量移植是促进受损中枢神经系统投射结构重建的一种有前景的策略。