Promoting directional axon growth from neural progenitors grafted into the injured spinal cord.
Promoting directional axon growth from neural progenitors grafted into the injured spinal cord.
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DOI：
10.1002/jnr.22288
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发表时间：
2010-05-01
影响因子：
4.2
通讯作者：
Fischer, Itzhak
中科院分区：
文献类型：
--
作者：
Bonner, Joseph F.;Blesch, Armin;Neuhuber, Birgit;Fischer, Itzhak
关键词：
脊髓损伤（Spinal cord injury，SCI）是一种破坏性疾病，其特征在于轴突连接中断、轴突再生失败以及运动和感觉功能丧失。神经干细胞的治疗前景一直集中在细胞替代，但在移植到受损的CNS后获得神经元整合仍存在许多障碍。在这项研究中，我们调查了神经递质的身份和轴突生长潜力的神经前体细胞移植到成年大鼠的背柱损伤。我们发现，使用神经元和胶质限制性祖细胞（NRP和GRP）的组合产生移植物衍生的神经元和GABA能神经元内的损伤部位与最小的轴突延伸。脑源性神经营养因子（BDNF）的管理与移植促进适度轴突生长的移植细胞。与此相反，注射表达BDNF的慢病毒载体喙的损伤产生的神经营养因子梯度和促进轴突的定向生长长达9毫米。分析注射BDNF慢病毒（在2.5和5.0毫米）的动物显示出显着更多的轴突和显着较长的轴突比对照组动物注射GFP慢病毒。然而，只有5.0 mm BDNF组表现出在吻侧方向延伸的偏好。我们的结论是，NRP/GRP移植物可用于产生兴奋性和抑制性神经元，而神经营养因子梯度可以引导轴突生长从移植物衍生的神经元向假定的目标。它们一起可以作为局部回路的神经元细胞替代和神经元中继形成的构建块。
Spinal cord injury (SCI) is a devastating condition characterized by disruption of axonal connections, failure of axonal regeneration, and loss of motor and sensory function. The therapeutic promise of neural stem cells has been focused on cell replacement but many obstacles remain in getting neuronal integration following transplantation into the injured CNS. In this study we investigated the neurotransmitter identity and axonal growth potential of neural progenitors following grafting into adult rats with a dorsal column lesion. We found that using a combination of neuronal and glial restricted progenitors (NRP and GRP) produced graft-derived glutamatergic and GABAergic neurons within the injury site with minimal axonal extension. Administration of brain derived neurotrophic factor (BDNF) with the graft promoted modest axonal growth from grafted cells. In contrast, injecting a lentiviral vector expressing BDNF rostral to the injury generated a neurotrophin gradient and promoted directional growth of axons for up to 9 mm. Analysis of animals injected with BDNF lentivirus (at 2.5 and 5.0 mm) showed significantly more axons and significantly longer axons than in control animals injected with GFP lentivirus. However, only the 5.0 mm BDNF group showed preference for extension in the rostral direction. We concluded that NRP/GRP grafts can be used to produce excitatory and inhibitory neurons while neurotrophin gradients can guide axonal growth from graft-derived neurons toward putative targets. Together, they can serve as a building block for neuronal cell replacement of local circuits and formation of neuronal relays.
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影响因子：
5.3
作者：
Piantino, J.;Burdick, J. A.;Benowitz, L. I.
通讯作者：
Benowitz, L. I.
影响因子：
5.3
作者：
Mai, Junyu;Fok, Lee;Poo, Mu-ming
通讯作者：
Poo, Mu-ming
影响因子：
5.3
作者：
Han, SSW;Kang, DY;Fischer, I
通讯作者：
Fischer, I
影响因子：
16.2
作者：
MayerProschel, M;Kalyani, AJ;Rao, MS
通讯作者：
Rao, MS
DOI：
10.1177/1073858408331372
发表时间：
2009-04
期刊：
The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry
影响因子：
--
作者：
Darian-Smith C
通讯作者：
Darian-Smith C