Long-Term Changes in Axon Calibers after Injury: Observations on the Mouse Corticospinal Tract.
Long-Term Changes in Axon Calibers after Injury: Observations on the Mouse Corticospinal Tract.
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DOI：
10.3390/ijms23137391
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发表时间：
2022-07-02
影响因子：
5.6
通讯作者：
中科院分区：
文献类型：
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作者：
白质病理在广泛的神经疾病中很常见。确定这种病理特征对于从机制上理解神经系统疾病以及发展神经成像生物标记物都是重要的。尽管轴突口径可能因数量级不同而不同，但它们受到严格的调控，并与神经元功能有关，已有几种疾病及其模型报告了轴突口径的变化。在这项研究中，我们利用创伤性脑损伤的撞击加速模型(IA-TBI)，利用AiryScan和电子显微镜来评估小鼠皮质脊髓束轴突直径分布(ADD)的早期和晚期变化。我们发现轴突直径服从对数正态分布，其参数在损伤后发生显着变化。虽然IA-TBI导致第7天皮质脊髓轴突丢失30%，偏向较大的轴突，但在损伤后21天，我们发现轴突频率显著重新分布，这是由于大口径轴突减少而没有检测到退变。我们推测，ADD特征的变化可能反映了受损神经系统的功能适应。此外，我们发现ADD特征为区分受伤和未受伤的小鼠提供了一种准确的方法。通过组织学或新出现的神经成像手段探索与损伤相关的ADD信号可能提供一种更细微和更全面的方式来表征白质病理，也可能产生新的损伤生物标志物。
White matter pathology is common across a wide spectrum of neurological diseases. Characterizing this pathology is important for both a mechanistic understanding of neurological diseases as well as for the development of neuroimaging biomarkers. Although axonal calibers can vary by orders of magnitude, they are tightly regulated and related to neuronal function, and changes in axon calibers have been reported in several diseases and their models. In this study, we utilize the impact acceleration model of traumatic brain injury (IA-TBI) to assess early and late changes in the axon diameter distribution (ADD) of the mouse corticospinal tract using Airyscan and electron microscopy. We find that axon calibers follow a lognormal distribution whose parameters significantly change after injury. While IA-TBI leads to 30% loss of corticospinal axons by day 7 with a bias for larger axons, at 21 days after injury we find a significant redistribution of axon frequencies that is driven by a reduction in large-caliber axons in the absence of detectable degeneration. We postulate that changes in ADD features may reflect a functional adaptation of injured neural systems. Moreover, we find that ADD features offer an accurate way to discriminate between injured and non-injured mice. Exploring injury-related ADD signatures by histology or new emerging neuroimaging modalities may offer a more nuanced and comprehensive way to characterize white matter pathology and may also have the potential to generate novel biomarkers of injury.
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DOI：
10.1523/jneurosci.5103-10.2011
发表时间：
2011-03-30
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Greer JE;McGinn MJ;Povlishock JT
通讯作者：
Povlishock JT
影响因子：
3.1
作者：
Innocenti, Giorgio M.;Caminiti, Roberto
通讯作者：
Caminiti, Roberto
影响因子：
--
作者：
Scheler, Gabriele
通讯作者：
Scheler, Gabriele
影响因子：
5.7
作者：
Harkins KD;Beaulieu C;Xu J;Gore JC;Does MD
通讯作者：
Does MD
DOI：
10.1073/pnas.0907655106
发表时间：
2009-11-17
影响因子：
11.1
作者：
Caminiti, Roberto;Ghaziri, Hassan;Innocenti, Giorgio M.
通讯作者：
Innocenti, Giorgio M.