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Matrix Deformation with Ectopic Cells Induced by Rotational Motion in Bioengineered Neural Tissues.
Annals of Biomedical Engineering ( IF 3.8 ) Pub Date : 2020-07-15 , DOI: 10.1007/s10439-020-02561-6
Nicolas Rouleau 1, 2, 3 , Nirosha J Murugan 1, 3, 4 , William Rusk 1 , Cole Koester 1 , David L Kaplan 1, 2, 3
Affiliation  

The brain’s extracellular matrix (ECM) is a dynamic protein-based scaffold within which neural networks can form, self-maintain, and re-model. When the brain incurs injuries, microscopic tissue tears and active ECM re-modelling give way to abnormal brain structure and function including the presence of ectopic cells. Post-mortem and neuroimaging data suggest that the brains of jet pilots and astronauts, who are exposed to rotational forces, accelerations, and microgravity, display brain anomalies which could be indicative of a mechanodisruptive pathology. Here we present a model of non-impact-based brain injury induced by matrix deformation following mechanical shaking. Using a bioengineered 3D neural tissue platform, we designed a repetitive shaking paradigm to simulate subtle rotational acceleration. Our results indicate shaking induced ectopic cell clustering that could be inhibited by physically restraining tissue movement. Imaging revealed that the collagen substrate surrounding cells was deformed following shaking. Applied to neonatal rat brains, shaking induced deformation of extracellular spaces within the cerebral cortices and reduced the number of cell bodies at higher accelerations. We hypothesize that ECM deformation may represent a more significant role in brain injury progression than previously assumed and that the present model system contributes to its understanding as a phenomenon.



中文翻译:

生物工程神经组织中由旋转运动引起的异位细胞基质变形。

大脑的细胞外基质 (ECM) 是一种基于蛋白质的动态支架,神经网络可以在其中形成、自我维持和重新建模。当大脑受伤时,微观组织撕裂和活跃的 ECM 重塑让位于异常的大脑结构和功能,包括异位细胞的存在。验尸和神经影像数据表明,暴露于旋转力、加速度和微重力的喷气式飞行员和宇航员的大脑会出现大脑异常,这可能表明存在机械破坏性病理。在这里,我们提出了一种由机械摇动后基质变形引起的非冲击性脑损伤模型。使用生物工程 3D 神经组织平台,我们设计了一个重复振动范式来模拟细微的旋转加速度。我们的结果表明震动诱导的异位细胞聚集可以通过物理限制组织运动来抑制。成像显示细胞周围的胶原基质在摇动后变形。应用于新生大鼠大脑,摇动诱导大脑皮层内细胞外空间的变形,并在更高的加速度下减少细胞体的数量。我们假设 ECM 变形在脑损伤进展中可能比以前假设的更重要,并且本模型系统有助于将其理解为一种现象。摇动诱导大脑皮层内细胞外空间的变形,并在更高的加速度下减少细胞体的数量。我们假设 ECM 变形在脑损伤进展中可能比以前假设的更重要,并且本模型系统有助于将其理解为一种现象。摇动诱导大脑皮层内细胞外空间的变形,并在更高的加速度下减少细胞体的数量。我们假设 ECM 变形在脑损伤进展中可能比以前假设的更重要,并且本模型系统有助于将其理解为一种现象。

更新日期:2020-07-15
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