Vögelin E, Baker J M, Gates J, Dixit V, Constantinescu M A, Jones N F
UCLA Hand Center, Department of Orthopaedic Surgery, Division of Plastic and Reconstructive Surgery, University of California, Los Angeles, CA 90024, USA.
Exp Neurol. 2006 Jun;199(2):348-53. doi: 10.1016/j.expneurol.2005.12.029. Epub 2006 Feb 17.
The purpose of this study was to evaluate the effect of continuously released BDNF on peripheral nerve regeneration in a rat model. Initial in vitro evaluation of calcium alginate prolonged-release-capsules (PRC) proved a consistent release of BDNF for a minimum of 8 weeks. In vivo, a worst case scenario was created by surgical removal of a 20-mm section of the sciatic nerve of the rat. Twenty-four autologous fascia tubes were filled with calcium alginate spheres and sutured to the epineurium of both nerve ends. The animals were divided into 3 groups. In group 1, the fascial tube contained plain calcium alginate spheres. In groups 2 and 3, the fascial tube contained calcium alginate spheres with BDNF alone or BDNF stabilized with bovine serum albumin, respectively. The autocannibalization of the operated extremity was clinically assessed and documented in 12 additional rats. The regeneration was evaluated histologically at 4 weeks and 10 weeks in a blinded manner. The length of nerve fibers and the numbers of axons formed in the tube was measured. Over a 10-week period, axons have grown significantly faster in groups 2 and 3 with continuously released BDNF compared to the control. The rats treated with BDNF (groups 2 and 3) demonstrated significantly less autocannibalization than the control group (group 1). These results suggest that BDNF may not only stimulate faster peripheral nerve regeneration provided there is an ideal, biodegradable continuous delivery system but that it significantly reduces the neuropathic pain in the rat model.
本研究的目的是评估持续释放的脑源性神经营养因子（BDNF）对大鼠模型中周围神经再生的影响。对海藻酸钙缓释胶囊（PRC）进行的初步体外评估证明，BDNF能持续释放至少8周。在体内，通过手术切除大鼠坐骨神经的20毫米节段，制造了一种最坏情况的场景。将24根自体筋膜管填充上海藻酸钙球，并缝合到神经两端的神经外膜上。将动物分为3组。第1组中，筋膜管内装有普通海藻酸钙球。在第2组和第3组中，筋膜管分别装有单独的BDNF或用牛血清白蛋白稳定化的BDNF的海藻酸钙球。对另外12只大鼠的手术肢体的自残情况进行了临床评估并记录。在第4周和第10周以盲法进行组织学评估再生情况。测量管内形成的神经纤维长度和轴突数量。在10周的时间里，与对照组相比，在持续释放BDNF的第2组和第3组中，轴突生长明显更快。用BDNF治疗的大鼠（第2组和第3组）的自残情况明显少于对照组（第1组）。这些结果表明，BDNF不仅在有理想的、可生物降解的持续递送系统时可能刺激周围神经更快再生，而且能显著减轻大鼠模型中的神经性疼痛。
