大脑成熟和神经系统疾病与微观结构变化密切相关,这些变化固有地影响大脑的机械行为。动物模型经常用于探索相对脑硬度变化作为潜在微观结构的函数。这里,我们使用cubrizone小鼠模型研究了在15周的观察期内由急性和慢性脱髓鞘引起的压痕引起的僵硬度变化.我们专注于call体,扣带,和皮质经历不同程度的去髓鞘和髓鞘再生,因此,导致特定区域的刚度变化。在未经治疗的小鼠中,call体的平均刚度从1.1±0.3kPa开始,然后,铜带治疗导致刚度下降到0.6±0.1kPa到第3周,暂时增加到0.9±0.3kPa到第6周,并最终稳定在0.7±0.1kPa到第9周的其余观察期间。扣带开始于3.2±0.9kPa,然后在第3周下降到1.6±0.4kPa,然后在第9周逐渐稳定在1.4±0.3kPa左右。皮质刚度总体上表现出较小的刚度变化;它开始于4.2±1.3kPa,到第3周下降到2.4±0.6kPa,到第6周稳定在2.7±0.9kPa左右。我们还评估了组织固定对基于压痕的机械组织表征的影响。一方面,固定会使未治疗的平均组织硬度急剧增加3.3倍,2.9对于扣带,皮层为3.6;另一方面,固定影响脱髓鞘过程中的区域间刚度比,因此表明固定对单个脑组织的影响不同。最后,我们确定了硬度测量值与髓鞘密度之间的空间相关性,并观察了髓鞘含量与组织硬度之间的区域特异性比例.重要声明:尽管开展了大量工作,大脑微观结构与机械行为之间的关系仍然未知。此外,文献中报道的测量结果的现有变化需要深入研究单个细胞和蛋白质群体对组织硬度和区域间硬度比的影响.这里,我们使用微压痕测量显示,在基于铜带的脱髓鞘小鼠模型中,脑硬度随髓磷脂密度而变化.此外,由于文献报道的结果相互矛盾,我们探讨了在机械表征之前组织固定的影响.我们观察到固定对我们的三个感兴趣区域有明显不同的影响,从而导致特定区域的组织僵硬,更重要的是,变化的区域间刚度比。
Brain maturation and neurological diseases are intricately linked to microstructural changes that inherently affect the brain\'s mechanical behavior. Animal models are frequently used to explore relative brain stiffness changes as a function of underlying microstructure. Here, we are using the cuprizone mouse model to study indentation-derived stiffness changes resulting from acute and chronic demyelination during a 15-week observation period. We focus on the corpus callosum,
cingulum, and cortex which undergo different degrees of de- and remyelination and, therefore, result in region-specific stiffness changes. Mean stiffness of the corpus callosum starts at 1.1 ± 0.3 kPa in untreated mice, then cuprizone treatment causes stiffness to drop to 0.6 ± 0.1 kPa by week 3, temporarily increase to 0.9 ± 0.3 kPa by week 6, and ultimately stabilize around 0.7 ± 0.1 kPa by week 9 for the rest of the observation period. The
cingulum starts at 3.2 ± 0.9 kPa, then drops to 1.6 ± 0.4 kPa by week 3, and then gradually stabilizes around 1.4 ± 0.3 kPa by week 9. Cortical stiffness exhibits less stiffness variations overall; it starts at 4.2 ± 1.3 kPa, drops to 2.4 ± 0.6 kPa by week 3, and stabilizes around 2.7 ± 0.9 kPa by week 6. We also assess the impact of tissue fixation on indentation-based mechanical tissue characterization. On the one hand, fixation drastically increases untreated mean tissue stiffness by a factor of 3.3 for the corpus callosum, 2.9 for the
cingulum, and 3.6 for the cortex; on the other hand, fixation influences interregional stiffness ratios during demyelination, thus suggesting that fixation affects individual brain tissues differently. Lastly, we determine the spatial correlation between stiffness measurements and myelin density and observe a region-specific proportionality between myelin content and tissue stiffness. STATEMENT OF SIGNIFICANCE: Despite extensive work, the relationship between microstructure and mechanical behavior in the brain remains mostly unknown. Additionally, the existing variation of measurement results reported in literature requires in depth investigation of the impact of individual cell and protein populations on tissue stiffness and interregional stiffness ratios. Here, we used microindentation measurements to show that brain stiffness changes with myelin density in the cuprizone-based demyelination mouse model. Moreover, we explored the impact of tissue fixation prior to mechanical characterization because of conflicting results reported in literature. We observe that fixation has a distinctly different impact on our three regions of interest, thus causing region-specific tissue stiffening and, more importantly, changing interregional stiffness ratios.