Bretzner Frederic, Liu Jie, Currie Erin, Roskams A Jane, Tetzlaff Wolfram
ICORD (International Collaboration On Repair Discoveries), Department of Zoology, University of British Columbia, Vancouver, BC, Canada.
Eur J Neurosci. 2008 Nov;28(9):1795-807. doi: 10.1111/j.1460-9568.2008.06462.x.
Transplantations of olfactory ensheathing cells (OECs) have been reported to promote axonal regeneration and functional recovery after spinal cord injury, but have demonstrated limited growth promotion of rat rubrospinal axons after a cervical dorsolateral funiculus crush. Rubrospinal neurons undergo massive atrophy after cervical axotomy and show only transient expression of regeneration-associated genes. Cell body treatment with brain-derived neurotrophic factor (BDNF) prevents this atrophy, stimulates regeneration-associated gene expression and promotes regeneration of rubrospinal axons into peripheral nerve transplants. Here, we hypothesized that the failure of rubrospinal axons to regenerate through a bridge of OEC transplants was due to this weak intrinsic cell body response. Hence, we combined BDNF treatment of rubrospinal neurons with transplantation of highly enriched OECs derived from the nasal mucosa and assessed axonal regeneration as well as behavioral changes after a cervical dorsolateral funiculus crush. Each treatment alone as well as their combination prevented the dieback of the rubrospinal axons, but none of them promoted rubrospinal regeneration beyond the lesion/transplantation site. Motor performance in a food-pellet reaching test and forelimb usage during vertical exploration (cylinder test) were more impaired after combining transplantation of OECs with BDNF treatment. This impaired motor performance correlated with lowered sensory thresholds in animals receiving the combinatorial therapy - which were not seen with each treatment alone. Only this combinatorial treatment group showed enhanced sprouting of calcitonin gene-related peptide-positive axons rostral to the lesion site. Hence, some combinatorial treatments, such as OECs with BDNF, may have undesired effects in the injured spinal cord.
据报道，嗅鞘细胞（OECs）移植可促进脊髓损伤后轴突再生和功能恢复，但在颈背外侧索挤压伤后，对大鼠红核脊髓轴突的生长促进作用有限。颈髓切断术后，红核脊髓神经元会发生大量萎缩，且仅短暂表达再生相关基因。用脑源性神经营养因子（BDNF）处理细胞体可防止这种萎缩，刺激再生相关基因表达，并促进红核脊髓轴突向周围神经移植物的再生。在此，我们假设红核脊髓轴突未能通过OEC移植桥再生是由于这种内在的细胞体反应较弱。因此，我们将BDNF处理红核脊髓神经元与移植源自鼻黏膜的高度富集的OECs相结合，并评估颈背外侧索挤压伤后的轴突再生以及行为变化。单独的每种处理及其组合均能防止红核脊髓轴突的回缩，但均未促进红核脊髓轴突在损伤/移植部位以外的再生。在食物颗粒抓取试验中的运动表现以及垂直探索（圆筒试验）期间的前肢使用情况，在将OECs移植与BDNF处理相结合后受损更严重。这种受损的运动表现与接受联合治疗的动物感觉阈值降低相关——单独的每种治疗均未出现这种情况。只有这个联合治疗组在损伤部位上方显示降钙素基因相关肽阳性轴突的芽生增强。因此，一些联合治疗，如OECs与BDNF联合，可能会对损伤的脊髓产生不良影响。
