Strain and rate-dependent neuronal injury in a 3D in vitro compression model of traumatic brain injury.
Strain and rate-dependent neuronal injury in a 3D in vitro compression model of traumatic brain injury.
复制标题
DOI：
10.1038/srep30550
复制
发表时间：
2016-08-02
影响因子：
4.6
通讯作者：
Franck C
中科院分区：
文献类型：
--
作者：
Bar-Kochba E;Scimone MT;Estrada JB;Franck C
在美国，每年报告超过170万例创伤性脑损伤，但仍然缺乏细胞损伤与冲击组织应变的预测相关性，特别是对于由压迫引起的神经元损伤。鉴于压缩变形在大多数钝性头部创伤中的普遍性，这一信息对于未来缓解和诊断策略的发展至关重要。使用三维体外神经元压缩模型，我们研究了冲击应变和应变率对神经元寿命，活力和病理形态学的作用。我们发现，应变幅度和速率有深刻的，但明显不同的损伤病理学的影响。应变大小影响神经元死亡的时间，而应变率影响群体损伤的病理形态学和程度。细胞损伤不是通过细胞骨架的局部变形而开始的，而是由整个细胞上的过度应变驱动的。此外，我们发现，机械穿孔，在拉伸和剪切神经元损伤的关键病理触发机制之一，没有观察到压缩。
In the United States over 1.7 million cases of traumatic brain injury are reported yearly, but predictive correlation of cellular injury to impact tissue strain is still lacking, particularly for neuronal injury resulting from compression. Given the prevalence of compressive deformations in most blunt head trauma, this information is critically important for the development of future mitigation and diagnosis strategies. Using a 3D in vitro neuronal compression model, we investigated the role of impact strain and strain rate on neuronal lifetime, viability, and pathomorphology. We find that strain magnitude and rate have profound, yet distinctively different effects on the injury pathology. While strain magnitude affects the time of neuronal death, strain rate influences the pathomorphology and extent of population injury. Cellular injury is not initiated through localized deformation of the cytoskeleton but rather driven by excess strain on the entire cell. Furthermore we find that, mechanoporation, one of the key pathological trigger mechanisms in stretch and shear neuronal injuries, was not observed under compression.