Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells
Robust growth of chronically injured spinal cord axons induced by grafts of genetically modified NGF-secreting cells
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DOI：
10.1006/exnr.1997.6704
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发表时间：
1997-12-01
影响因子：
5.3
通讯作者：
Tuszynski, MH
中科院分区：
文献类型：
--
作者：
Grill, RJ;Blesch, A;Tuszynski, MH
中枢神经系统急性和慢性损伤后很少有轴突自发再生。以前我们已经证明，向急性损伤的脊髓持续局部输送神经营养因子可诱导脊髓和脊髓神经元的稳健生长。在本研究中，我们检查了慢性损伤的轴突是否也表现出显著的神经营养素反应性。成年大鼠进行双侧背侧半切病变，轴突切断下行脊髓上途径，包括皮质脊髓，红核脊髓，和铜蓝脊髓束，和上行背侧脊髓感觉投射。一到三个月后，受伤的大鼠接受了同系成纤维细胞的移植，这些细胞经过基因修饰可以产生神经生长因子（NGF）。对照受试者接受未修饰的细胞移植物或转导细胞以表达报告基因β-半乳糖苷酶。移植后3至5个月，接受神经生长因子分泌移植物的动物显示出假定的铜蓝脊髓轴突和背外侧束的初级感觉轴突密集生长到移植病变部位。未检测到皮质脊髓、中缝脊神经和局部运动轴突的生长。因此，在脊髓损伤后的慢性阶段，通过局部的、连续的神经营养因子转基因递送，可以引起脊髓上和脊髓轴突的限定群体的稳健生长。(C)北京：科学出版社.
Little spontaneous regeneration of axons occurs after acute and chronic injury to the CNS. Previously we have shown that the continuous local delivery of neurotropic factors to the acutely injured spinal cord induces robust growth of spinal and. supraspinal axons, In the present study we examined whether chronically injured axons also demonstrate significant neurotrophin responsiveness. Adult rats underwent bilateral dorsal hemisection lesions that axotomize descending supraspinal pathways, including the corticospinal, rubrospinal, and cerulospinal tracts, and ascending dorsal spinal sensory projections. One to three months later, injured rats received grafts of syngenic fibroblasts genetically modified to produce nerve growth factor (NGF). Control subjects received unmodified cell grafts or cells transduced to express the reporter gene beta-galactosidase, Three to five months after grafting, animals that received NGF-secreting grafts showed dense growth of putative cerulospinal axons and primary sensory axons of the dorsolateral fasciculus into the grafted lesion site. Growth from corticospinal, raphaespinal, and local motor axons was not detected. Thus, robust growth of defined populations of supraspinal and spinal axons can be elicited in chronic stages after spinal cord injury by localized, continuous transgenic delivery of neurotrophic factors. (C) 1997 Academic Press.