Local and remote growth factor effects after primate spinal cord injury.
Local and remote growth factor effects after primate spinal cord injury.
复制标题
DOI：
10.1523/jneurosci.1924-10.2010
复制
发表时间：
2010-07-21
期刊：
影响因子：
--
通讯作者：
Tuszynski MH
中科院分区：
文献类型：
--
作者：
Brock JH;Rosenzweig ES;Blesch A;Moseanko R;Havton LA;Edgerton VR;Tuszynski MH
灵长类动物的脊髓损伤模型在几个方面不同于啮齿类动物模型，包括脊髓投射的相对大小和功能性神经解剖学。规模上的根本差异提高了逆行损伤信号的可能性，以及在啮齿动物中表现出疗效的脊髓水平上应用的治疗，可能无法影响灵长类系统中更远距离的神经元。因此，我们研究了本地和远程神经元的反应神经营养因子分泌细胞移植物内放置在网站的权利C7半切病变的猕猴。6个月后的BDNF和NT-3的基因传递到C7病变部位，我们发现两个本地的轴突生长的生长因子的影响，和远程的生长因子的影响反映在轴突切断引起的萎缩的大锥体神经元内的主要运动皮层显着减少。在啮齿动物模型中的进一步研究表明，BDNF，而不是NT-3，介导了大脑中皮质脊髓神经元的远程保护。因此，受损的神经系统保留了在灵长类CNS的延伸距离上响应生长信号的能力，促进局部轴突生长并防止远处病变诱导的神经元变性。脊髓给药的生长因子的远距离皮质效应可以“激发”神经元对促进轴突可塑性或再生的实验疗法作出反应。
Primate models of spinal cord injury differ from rodent models in several respects, including the relative size and functional neuroanatomy of spinal projections. Fundamental differences in scale raise the possibility that retrograde injury signals, and treatments applied at the level of the spinal cord that exhibit efficacy in rodents, may fail to influence neurons at the far greater distances of primate systems. Thus, we examined both local and remote neuronal responses to neurotrophic factor-secreting cell grafts placed within sites of right C7 hemisection lesions in the rhesus macaque. Six months after gene delivery of BDNF and NT-3 into C7 lesion sites, we found both local effects of growth factors on axonal growth, and remote effects of growth factors reflected in significant reductions in axotomy-induced atrophy of large pyramidal neurons within the primary motor cortex. Further examination in a rodent model suggested that BDNF, rather than NT-3, mediated remote protection of corticospinal neurons in the brain. Thus, injured neural systems retain the ability to respond to growth signals over the extended distances of the primate CNS, promoting local axonal growth and preventing lesion-induced neuronal degeneration at a distance. Remote cortical effects of spinally-administered growth factors could “prime” the neuron to respond to experimental therapies that promote axonal plasticity or regeneration.