Gillon Russell S, Cui Qi, Dunlop Sarah A, Harvey Alan R
School of Anatomy and Human Biology, The Western Australian Institute for Medical Research, The University of Western Australia, Crawley, Perth, Australia.
J Neurosci Res. 2003 Nov 15;74(4):524-32. doi: 10.1002/jnr.10788.
Analysis of the effectiveness of allografts and immunosuppression in the repair of nerve defects in the adult peripheral nervous system (PNS) has a long experimental and clinical history. There is little information, however, on the use of allografts in peripheral nerve (PN) transplantation into the injured central nervous system (CNS). We assessed the ability of PN allografts (from Dark-Agouti rats) to support regeneration of adult rat retinal ganglion cell (RGC) axons in immunosuppressed host Lewis rats. PN allografts were sutured onto intraorbitally transected optic nerves. Three weeks after grafting, regenerating RGC axon numbers were determined using retrograde fluorescent labelling, and total axons within PN grafts were assessed using pan-neurofilament immunohistochemistry. In the absence of immunosuppression, PN allografts contained few axons and there were very few labelled RGC. These degenerate grafts contained many T cells and macrophages. Systemic (intraperitoneal) application of the immunosuppressants cyclosporin-A or FK506 reduced cellular infiltration into allografts and resulted in extensive axonal regrowth from surviving RGCs. The average number of RGCs regenerating axons into immunosuppressed allografts was not significantly different from that seen in PN autografts in rats sham-injected with saline. Many pan-neurofilament-positive axons, a proportion of which were myelinated, were seen in immunosuppressed allografts, particularly in proximal regions of the grafts toward the optic nerve-PN interface. This study demonstrates that PN allografts can support axonal regrowth in immunosuppressed adult hosts, and points to possible clinical use in CNS repair.
对同种异体移植物及免疫抑制在成人外周神经系统（PNS）神经缺损修复中的有效性分析已有漫长的实验和临床历史。然而，关于将同种异体移植物用于外周神经（PN）移植到受损中枢神经系统（CNS）的信息却很少。我们评估了PN同种异体移植物（来自黑褐大鼠）在免疫抑制的宿主Lewis大鼠中支持成年大鼠视网膜神经节细胞（RGC）轴突再生的能力。将PN同种异体移植物缝合到经眶内横断的视神经上。移植三周后，使用逆行荧光标记法测定再生的RGC轴突数量，并使用泛神经丝免疫组织化学法评估PN移植物内的总轴突数量。在没有免疫抑制的情况下，PN同种异体移植物中轴突很少，标记的RGC也很少。这些退化的移植物含有许多T细胞和巨噬细胞。全身（腹腔内）应用免疫抑制剂环孢素A或FK506可减少细胞浸润到同种异体移植物中，并导致存活的RGC大量轴突再生。再生轴突进入免疫抑制同种异体移植物的RGC平均数量与假注射生理盐水的大鼠PN自体移植物中的数量无显著差异。在免疫抑制的同种异体移植物中可见许多泛神经丝阳性轴突，其中一部分有髓鞘，特别是在移植物靠近视神经-PN界面的近端区域。本研究表明，PN同种异体移植物可在免疫抑制的成年宿主中支持轴突再生，并指出其在CNS修复中可能的临床应用。
