Vavrek Romana, Pearse Damien D, Fouad Karim
Faculty of Rehabilitation Medicine, University of Alberta, Edmonton, Canada.
J Neurotrauma. 2007 Oct;24(10):1667-73. doi: 10.1089/neu.2007.0290.
Axonal regeneration after spinal cord injury (SCI) in adult mammals is limited by inhibitors associated with myelin and the glial scar. To overcome these inhibitors, a combined approach will be required. We have previously demonstrated that, following complete SCI in rats, a combination of bridging the lesion with Schwann cell (SC)-filled guidance channels, olfactory ensheathing glia implantation, and chondroitinase ABC delivery promoted regeneration of serotonergic fibers into the lumbar spinal cord. In addition, this combined treatment significantly improved locomotor recovery. To complement these findings, we repeated this combined treatment to assess whether fibers other than serotonergic axons were able to regenerate into the caudal spinal cord. In this experiment, we injected the retrograde tracer FluoroGold (FG) into the spinal cord caudal to a complete transection in a control and a treated group. FG-positive cells rostral to the lesion and in the brainstem of animals in the treated group showed that axons were able to regenerate across the SC bridge and into the caudal spinal cord. Treated rats had labeled cells in the reticulospinal nuclei, vestibular nuclei, and the raphe nucleus as well as in the spinal cord. Cell numbers were highest in the thoracic spinal cord and the lateral vestibular nucleus. Determining the mechanisms for the superior capability of these cell populations to regenerate may provide valuable clues in the design of future treatment approaches.
成年哺乳动物脊髓损伤(SCI)后的轴突再生受到与髓磷脂和胶质瘢痕相关的抑制剂的限制。为了克服这些抑制剂,需要采用联合方法。我们之前已经证明,在大鼠完全性脊髓损伤后,将充满雪旺细胞(SC)的引导通道桥接损伤部位、植入嗅鞘胶质细胞以及递送软骨素酶ABC的联合方法促进了5-羟色胺能纤维向腰段脊髓的再生。此外,这种联合治疗显著改善了运动功能恢复。为了补充这些发现,我们重复了这种联合治疗,以评估除5-羟色胺能轴突外的其他纤维是否能够再生进入尾段脊髓。在本实验中,我们将逆行示踪剂荧光金(FG)注射到对照组和治疗组完全横断部位尾侧的脊髓中。治疗组动物损伤部位头侧和脑干中的FG阳性细胞表明轴突能够穿过SC桥并再生进入尾段脊髓。治疗后的大鼠在网状脊髓核、前庭核、中缝核以及脊髓中都有标记细胞。细胞数量在胸段脊髓和外侧前庭核中最多。确定这些细胞群再生能力更强的机制可能为未来治疗方法的设计提供有价值的线索。