Department of Bioengineering, University of Texas at Arlington, Arlington, TX, United States.
Department of Biomedical Engineering, Rochester Institute of Technology, Rochester, NY, United States.
Sci Rep. 2020 Feb 20;10(1):3054. doi: 10.1038/s41598-020-59888-2.
Brain injuries caused by an explosive blast or blunt force is typically presumed to associate with mechanical trauma to the brain tissue. Recent findings from our laboratory suggest that shockwaves produced by a blast can generate micron-sized bubbles in the tissue. The collapse of microbubbles (i.e., microcavitation) may induce a mechanical trauma and compromise the integrity of the blood-brain endothelium (BBE). To test our hypothesis, we engineered a BBE model to determine the effect of microbubbles on the structural and functional changes in the BBE. Using monolayers of mouse primary brain microvascular endothelial cells, the permeability coefficient was measured following simulated blast-induced microcavitation. This event down-regulated the expression of tight junction markers, disorganized the cell-cell junction, and increased permeability. Since poloxamers have been shown to rescue damaged cells, the cells were treated with the FDA-approved poloxamer 188 (P188). The results indicate P188 recovered the permeability, restored the tight junctions, and suppressed the expressions of matrix metalloproteinases. The biomimetic interface we developed appears to provide a systematic approach to replicate the structure and function of BBE, determine its alteration in response to traumatic brain injury, and test potential therapeutic treatments to repair the damaged brain endothelium.
由爆炸或钝力引起的脑损伤通常被认为与脑组织的机械性创伤有关。我们实验室的最新发现表明，爆炸产生的冲击波会在组织中产生微米大小的气泡。微泡的崩溃（即微空化）可能会引起机械性创伤，并损害血脑内皮（BBE）的完整性。为了验证我们的假设，我们设计了一种 BBE 模型，以确定微泡对 BBE 的结构和功能变化的影响。使用小鼠原代脑微血管内皮细胞的单层，在模拟爆炸诱导的微空化后测量通透性系数。这一事件下调了紧密连接标记物的表达，使细胞-细胞连接紊乱，并增加了通透性。由于已经证明泊洛沙姆可以挽救受损细胞，因此用美国食品和药物管理局批准的泊洛沙姆 188（P188）处理细胞。结果表明，P188 恢复了通透性，修复了紧密连接，并抑制了基质金属蛋白酶的表达。我们开发的仿生界面似乎提供了一种系统的方法来复制 BBE 的结构和功能，确定其在创伤性脑损伤中的变化，并测试潜在的治疗方法来修复受损的脑内皮。
