Department of Bioengineering , University of Texas at Arlington , Arlington , Texas 76019 , United States.
ACS Appl Mater Interfaces. 2019 Feb 6;11(5):4889-4899. doi: 10.1021/acsami.8b21410. Epub 2019 Jan 25.
Blast-induced traumatic brain injury (bTBI) can result in cell/tissue damage and lead to clinical and neuropsychiatric symptoms. Shock waves from a blast propagate through the brain and initiate cascades of mechanical and physiological events that can adversely affect the brain function. Although studies using animal models and brain slices have shown macroscale changes in the brain tissue in response to blast, systematic elucidation of coupling mechanisms is currently lacking. One mechanism that has been postulated and demonstrated repeatedly is the blast-induced generation and subsequent collapse of micron-size bubbles (i.e., microcavitation). Using a custom-designed exposure system, we have previously reported that upon collapsing of microbubbles, astrocytes exhibited changes in the cell viability, cellular biomechanics, production of reactive oxygen species, and activation of apoptotic signaling pathways. In this paper, we have applied microfabrication techniques and seeded astrocytes in a spatially controlled manner to determine the extent of cell damage from the site of the collapse of microbubbles. Such a novel experimental design is proven to facilitate our effort to examine the altered cell viability and functionality by monitoring the transient calcium spiking activity in real-time. We now report that the effect of microcavitation depends on the distance from which cells are seeded, and the cell functionality assessed by calcium dynamics is significantly diminished in the cells located within ∼800 μm of the collapsing microbubbles. Both calcium influx across the cell membrane via N-type calcium channels and intracellular calcium store are altered in response to microcavitation. Finally, the FDA-approved poloxamer 188 (P188) was used to reconstitute the compromised cell membrane and restore the cell's reparative capability. This finding may lead to a feasible treatment for partially mitigating the tissue damage associated with bTBI.
爆炸伤性脑损伤 (bTBI) 可导致细胞/组织损伤，并引发临床和神经精神症状。爆炸产生的冲击波在大脑中传播，并引发一系列机械和生理事件，这些事件可能会对大脑功能产生不利影响。尽管使用动物模型和脑片的研究已经显示出脑组织对爆炸的宏观变化，但目前还缺乏对耦合机制的系统阐明。已经提出并反复证明的一种机制是爆炸诱导的微米级气泡（即微空化）的产生和随后的坍塌。使用定制设计的暴露系统，我们之前已经报道过，当微泡坍塌时，星形胶质细胞的细胞活力、细胞生物力学、活性氧的产生和细胞凋亡信号通路的激活发生变化。在本文中，我们应用微加工技术以空间控制的方式接种星形胶质细胞，以确定从微泡坍塌部位产生的细胞损伤程度。这种新颖的实验设计被证明有助于我们通过实时监测瞬态钙尖峰活动来检查改变的细胞活力和功能。我们现在报告说，微空化的效果取决于细胞接种的距离，并且位于距坍塌微泡约 800μm 范围内的细胞的钙动力学评估的细胞功能显著降低。微空化作用会改变通过 N 型钙通道跨细胞膜的钙内流和细胞内钙库。最后，使用经 FDA 批准的泊洛沙姆 188 (P188) 重建受损的细胞膜并恢复细胞的修复能力。这一发现可能为部分缓解与 bTBI 相关的组织损伤提供可行的治疗方法。
