Background

Axonal injury is a major component of traumatic spinal cord injury (SCI), associated with rapid deformation of spinal tissue and axonal projections. In vitro models enable us to examine these effects and screen potential therapies in a controlled, reproducible manner.

New method

A customized, stretchable microchannel system was developed using polydimethylsiloxane microchannels. Cortical and spinal embryonic rat neurons were cultured within the microchannel structures, allowing a uniaxial strain to be applied to isolated axonal processes. Global strains of up to 52% were applied to the stretchable microchannel-on-a-chip platform leading to local strains of up to 12% being experienced by axons isolated in the microchannels.

Results

Individual axons exposed to local strains between 3.2% and 8.7% developed beading within 30-minutes of injury. At higher local strains of 9.8% and 12% individual axons ruptured within 30-minutes of injury. Axon bundles, or fascicles, were more resistant to rupture at each strain level, compared to individual axons. At lower local strain of 3.2%, axon bundles inside microchannels and neuronal cells near entrances of them progressively swelled and degenerated over a period of 7 days after injury.

Comparison with existing method(s)

This method is simple, reliable and reproducible with good control and measurement of injury tolerance and morphological deformations using standard laboratory equipment. By measuring local strains, we observed that axonal injuries occur at a lower strain magnitude and a lower strain rate than previous methods reporting global strains, which may not accurately reflect the true axonal strain.

Conclusions

We describe a novel stretchable microchannel-on-a-chip platform to study the effect of varying local strain on morphological characteristics of neuronal injury.

中文翻译：

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可拉伸微通道芯片：评估单轴应变对神经元损伤影响的简单模型

背景

轴索损伤是创伤性脊髓损伤 (SCI) 的主要组成部分，与脊髓组织的快速变形和轴突突起有关。体外模型使我们能够以可控的、可重复的方式检查这些影响并筛选潜在的治疗方法。

新方法

使用聚二甲基硅氧烷微通道开发了一种定制的可拉伸微通道系统。皮层和脊髓胚胎大鼠神经元在微通道结构内培养，允许将单轴应变应用于孤立的轴突过程。高达 52% 的全局应变应用于可拉伸的微通道芯片平台，导致微通道中分离的轴突承受高达 12% 的局部应变。

结果

暴露于 3.2% 和 8.7% 之间的局部应变的个体轴突在损伤后 30 分钟内形成珠状。在 9.8% 和 12% 的较高局部应变下，单个轴突在受伤后 30 分钟内破裂。与单个轴突相比，轴突束或束在每个应变水平上都更能抵抗破裂。在 3.2% 的较低局部应变下，微通道内的轴突束和它们入口附近的神经元细胞在受伤后的 7 天内逐渐膨胀和退化。

与现有方法的比较

该方法简单、可靠且可重复，使用标准实验室设备可以很好地控制和测量损伤耐受性和形态变形。通过测量局部应变，我们观察到与以前报告全局应变的方法相比，轴突损伤发生在较低的应变幅度和较低的应变率下，这可能无法准确反映真实的轴突应变。

结论

我们描述了一种新型可拉伸微通道芯片平台，以研究不同局部应变对神经元损伤形态特征的影响。