High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model
High rate shear strain of three-dimensional neural cell cultures: a new in vitro traumatic brain injury model
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DOI：
10.1016/j.jbiomech.2004.05.032
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发表时间：
2005-05-01
影响因子：
2.4
通讯作者：
Cargill, RS
中科院分区：
文献类型：
--
作者：
LaPlaca, MC;Cullen, DK;Cargill, RS
产生耐受性和机械信息的创伤性脑损伤（TBI）的细胞培养模拟的保真度依赖于细胞模型和机械损伤参数两者。我们设计并表征了一种机电细胞剪切装置，以产生受控的高应变率损伤（高达0.50应变，30 s（-1）应变率），使三维（3-D）神经培养物（细胞外基质支架中的神经元或星形胶质细胞）变形。理论分析表明，这些参数在整个培养物中产生了一个异质的3-D应变场，该应变场依赖于基质内的初始细胞取向，从而导致正常应变和剪切应变的各种组合。通过在一系列应变和应变率的最大位移期间跟踪非细胞基质中的荧光微珠，验证了在一系列输入参数范围内创建线性剪切应变场的能力。此外，在大鼠皮质星形胶质细胞和神经元中，细胞死亡被证明是对高速率、高幅度剪切应变的响应。此外，细胞反应内的3-D神经元培养依赖于方向，与较高的预测剪切应变与增加损失的神经突，表明文化配置可能是一个重要的因素，在机械，因此细胞，响应创伤性侮辱。总的来说，这些结果表明，差异的反应存在于3-D文化受到机械损伤，也许模仿体内环境，这种新的模型可用于研究与TBI相关的复杂的细胞机制。(c)2004爱思唯尔有限公司保留所有权利。
The fidelity of cell culture simulations of traumatic brain injury (TBI) that yield tolerance and mechanistic information relies on both the cellular models and mechanical insult parameters. We have designed and characterized an electro-mechanical cell shearing device in order to produce a controlled high strain rate injury (up to 0.50 strain, 30 s(-1) strain rate) that deforms three-dimensional (3-D) neural cultures (neurons or astrocytes in an extracellular matrix scaffold). Theoretical analysis revealed that these parameters generate a heterogeneous 3-D strain field throughout the cultures that is dependent on initial cell orientation within the matrix, resulting in various combinations of normal and shear strain. The ability to create a linear shear strain field over a range of input parameters was verified by tracking fluorescent microbeads in an acellular matrix during maximal displacement for a range of strains and strain rates. In addition, cell death was demonstrated in rat cortical astrocytes and neurons in response to high rate, high magnitude shear strain. Furthermore, cell response within the 3-D neuronal cultures depended on orientation, with higher predicted shear strain correlating with an increased loss of neurites, indicating that culture configuration may be an important factor in the mechanical, and hence cellular, response to traumatic insults. Collectively, these results suggest that differential responses exist within a 3-D culture subjected to mechanical insult, perhaps mimicking the in vivo environment, and that this new model can be used to investigate the complex cellular mechanisms associated with TBI. (c) 2004 Elsevier Ltd. All rights reserved.