Single collateral reconstructions reveal distinct phases of corticospinal remodeling after spinal cord injury.

Single collateral reconstructions reveal distinct phases of corticospinal remodeling after spinal cord injury.
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DOI:
10.1371/journal.pone.0030461
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发表时间:
2012
期刊:
影响因子:
3.7
通讯作者:
Bareyre FM
Bareyre FM
中科院分区:
综合性期刊3区
文献类型:
--
作者:
Lang C;Guo X;Kerschensteiner M;Bareyre FM

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脊髓损伤通常会导致严重的功能缺陷,在不完全损伤的情况下,可以通过轴突重塑进行部分补偿。例如,皮质脊髓束(CST)对胸廓横断的反应是形成脊髓内迂回回路。迂回回路形成的关键步骤是颈髓中新的CST侧支与局部中间神经元接触。个别络脉是如何随着时间的推移而形成和完善的,人们还没有完全理解。我们在损伤后的不同时间点追踪后肢皮质脊髓束,以显示颈侧支形成开始于前10天。这些侧枝循环可以持续至少24周。有趣的是,主要和次要的CST成分有助于形成持久的CST抵押品。然后,我们开发了一种方法来标记单CST的基础上Cre重组酶的病毒基因转移到少量的皮质投射神经元在Thy 1-STP-YFP或Thy 1-Brainbow小鼠的侧枝。对损伤后12周的单个侧支循环的重建和分析显示,CST重塑分为3个阶段。侧支生长在损伤后的前10天开始。在损伤后10天至3-4周,在灰质中形成细长且高度分支的侧支,其复杂性取决于它们起源的CST组分。最后,在损伤后3-4周和12周之间,CST侧支的大小基本保持不变,而它们与中间神经元的接触模式成熟。这项研究提供了一个全面的解剖分析损伤后的CST重组,并揭示了CST重塑发生在不同的阶段。我们的研究结果和技术将有助于进一步阐明脊髓损伤后CST重塑的机制和促进功能恢复。
Injuries to the spinal cord often result in severe functional deficits that, in case of incomplete injuries, can be partially compensated by axonal remodeling. The corticospinal tract (CST), for example, responds to a thoracic transection with the formation of an intraspinal detour circuit. The key step for the formation of the detour circuit is the sprouting of new CST collaterals in the cervical spinal cord that contact local interneurons. How individual collaterals are formed and refined over time is incompletely understood. We traced the hindlimb corticospinal tract at different timepoints after lesion to show that cervical collateral formation is initiated in the first 10 days. These collaterals can then persist for at least 24 weeks. Interestingly, both major and minor CST components contribute to the formation of persistent CST collaterals. We then developed an approach to label single CST collaterals based on viral gene transfer of the Cre recombinase to a small number of cortical projection neurons in Thy1-STP-YFP or Thy1-Brainbow mice. Reconstruction and analysis of single collaterals for up to 12 weeks after lesion revealed that CST remodeling evolves in 3 phases. Collateral growth is initiated in the first 10 days after lesion. Between 10 days and 3–4 weeks after lesion elongated and highly branched collaterals form in the gray matter, the complexity of which depends on the CST component they originate from. Finally, between 3–4 weeks and 12 weeks after lesion the size of CST collaterals remains largely unchanged, while the pattern of their contacts onto interneurons matures. This study provides a comprehensive anatomical analysis of CST reorganization after injury and reveals that CST remodeling occurs in distinct phases. Our results and techniques should facilitate future efforts to unravel the mechanisms that govern CST remodeling and to promote functional recovery after spinal cord injury.
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发表时间: 2011-04-12
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