LaPlaca Michelle C, Lessing M Christian, Prado Gustavo R, Zhou Runzhou, Tate Ciara C, Geddes-Klein Donna, Meaney David F, Zhang Liying
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr., Atlanta, GA 030332-0535, USA.
Wallace H. Coulter Department of Biomedical Engineering, Georgia Institute of Technology and Emory University, 313 Ferst Dr., Atlanta, GA 030332-0535, USA.
Clin Biomech (Bristol). 2019 Apr;64:2-13. doi: 10.1016/j.clinbiomech.2018.05.016. Epub 2018 Jun 7.
An increases in plasma membrane permeability is part of the acute pathology of traumatic brain injury and may be a function of excessive membrane force. This membrane damage, or mechanoporation, allows non-specific flux of ions and other molecules across the plasma membrane, and may ultimately lead to cell death. The relationships among tissue stress and strain, membrane permeability, and subsequent cell degeneration, however, are not fully understood.
Fluorescent molecules of different sizes were introduced to the cerebrospinal fluid space prior to injury and animals were sacrificed at either 10 min or 24 h after injury. We compared the spatial distribution of plasma membrane damage following controlled cortical impact in the rat to the stress and strain tissue patterns in a 3-D finite element simulation of the injury parameters.
Permeable cells were located primarily in the ipsilateral cortex and hippocampus of injured rats at 10 min post-injury; however by 24 h there was also a significant increase in the number of permeable cells. Analysis of colocalization of permeability marker uptake and Fluorojade staining revealed a subset of permeable cells with signs of degeneration at 24 h, but plasma membrane damage was evident in the vast majority of degenerating cells. The regional and subregional distribution patterns of the maximum principal strain and shear stress estimated by the finite element model were comparable to the cell membrane damage profiles following a compressive impact.
These results indicate that acute membrane permeability is prominent following traumatic brain injury in areas that experience high shear or tensile stress and strain due to differential mechanical properties of the cell and tissue organization, and that this mechanoporation may play a role in the initiation of secondary injury, contributing to cell death.
质膜通透性增加是创伤性脑损伤急性病理过程的一部分，可能是膜力过大的结果。这种膜损伤，即机械穿孔，会使离子和其他分子非特异性地穿过质膜，最终可能导致细胞死亡。然而，组织应力和应变、膜通透性以及随后的细胞退变之间的关系尚未完全明确。
在损伤前将不同大小的荧光分子引入脑脊液空间，在损伤后10分钟或24小时处死动物。我们将大鼠控制性皮质撞击后质膜损伤的空间分布与损伤参数三维有限元模拟中的应力和应变组织模式进行了比较。
损伤后10分钟，通透性细胞主要位于受伤大鼠的同侧皮质和海马体；然而到24小时时，通透性细胞数量也显著增加。对通透性标记物摄取与氟玉染色共定位的分析显示，24小时时有一部分通透性细胞出现退变迹象，但绝大多数退变细胞中质膜损伤明显。有限元模型估计的最大主应变和剪应力的区域及亚区域分布模式与压缩撞击后的细胞膜损伤情况相符。
这些结果表明，由于细胞和组织结构的力学特性差异，创伤性脑损伤后，在承受高剪应力或拉应力及应变的区域，急性膜通透性显著增加，且这种机械穿孔可能在继发性损伤的起始过程中起作用，导致细胞死亡。
