脊髓夹伤是一类临床上常见的严重中枢神经损伤,主要病因是外力导致的脊椎椎骨骨折和椎管内肿瘤等。中国科学院遗传与发育生物学研究所戴建武研究员领导的再生医学实验室与南京市鼓楼医院神经外科合作,在脊髓夹伤后的神经再生研究中取得了重要进展。
脊髓夹伤后,胶原蛋白在损伤部位大量表达。戴建武实验室研制出了能与胶原蛋白特异结合的基因工程重组人脑源性神经营养因子(CBD-BDNF),提出了利用损伤部位的胶原蛋白作为结合靶点和再生支架的思路。
他们在大鼠脊髓夹闭伤模型中证明,脊髓夹伤部位的胶原蛋白可以作为CBD-BDNF的有效靶点。一次性鞘内注射的CBD-BDNF能较长时间地存留在损伤部位进行治疗。CBD-BDNF能够有效促进脊髓夹伤后神经电位的传导,神经再生和运动能力的恢复。戴建武研究员表示,该实验是脊髓损伤修复研究长期目标的又一次有效尝试,但这次更接近临床情况。
这项工作以戴建武实验室博士研究生韩倩倩和南京市鼓楼医院神经外科梁维帮为共同第一作者发表在Biomaterials杂志上。
遗传发育所戴建武研究员实验室主要从事干细胞和再生医学研究,近年来在包括神经再生和神经损伤修复等多个领域取得了多项研究成果。
推荐原文出处:
Biomaterials doi:10.1016/j.biomaterials.2010.07.084
The promotion of neurological recovery in the rat spinal cord crushed injury model by collagen-binding BDNF
Weibang Lianga, 1, Qianqian Hanb, c, 1, Wei Jina, Zhifeng Xiaob, Jingchun Huangd, Hongbin Nia, Bing Chenb, Jie Konga, Jun Wua and Jianwu Daib, ,
a Department of Neurosurgery, The Affiliated Drum Tower Hospital, School of Medicine, Nanjing University, Nanjing 210008, China
b Key laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing 100080, China
c Graduate School, Chinese Academy of Sciences, Beijing 100080, China
d Shandong Quality Inspection Center For Medical Devices, China State Drug Administration (SFDA), JiNan 250101, China
Spinal cord crushed injury is clinically common. Promoting targeted neural regeneration at the crushed site of spinal cord could be important for the repair. It has been demonstrated in our previous work that native human BDNF fused with a collagen-binding domain (CBD-BDNF) can bind to collagen specifically to exert the neurotrophic effect on promoting axonal regeneration. After injury, collagen is highly accumulated at the injury site. We thus speculate that CBD-BDNF will bind to the extracellular matrix collagen and concentrate at the injury site to improve the therapy. Using the rat spinal cord crushed injury model, we have found that CBD-BDNF by one-time intrathecally injection could be retained and concentrated at the injury site for a longer time than native BDNF without collagen-binding domain. CBD-BDNF could promote better neural regeneration and locomotion recovery.