Extracellular matrix deformations of the porcine recurrent laryngeal nerve in response to hydrostatic pressure.
Extracellular matrix deformations of the porcine recurrent laryngeal nerve in response to hydrostatic pressure.
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猪外喉神经的细胞外基质变形响应静水压力。
DOI：
10.1016/j.actbio.2022.09.039
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发表时间：
2022-11
影响因子：
9.7
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中科院分区：
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由邻近组织结构（例如主动脉）施加的超生理压迫或张力引起的喉返神经（RLN）损伤可能导致特发性单侧声带麻痹（iUVP）的发作，导致说话、呼吸和吞咽困难。我们之前在青春期猪中证明，右侧 RLN 神经外膜表现出均匀的脂肪组织成分，在颈部区域内沿其长度具有较大数量的脂肪组织，而左侧 RLN 在胸部区域显示出更多的胶原成分，在颈部区域显示出更多数量的脂肪组织。相比之下，仔猪的神经外膜主要由胶原组织组成，其沿左右 RLN 的长度保持均匀。对仔猪和猪的左、右 RLN 进行的拉伸测试显示，RLN 侧面和各节段的应变存在相关差异。本研究的目的是研究 RLN 的外部静水压如何影响神经的结缔组织和微观结构。从八头青春期猪和九头仔猪的远端（颈部/颈部）区域和近端（右 RLN 锁骨下，左 RLN 胸部）区域收获 RLN 节段。分离 RLN 节段并在流体压缩下进行评估，以测试有关神经外膜组成和对施加力的反应的假设。在 0、40 和 80 mmHg 的压力下进行神经外膜胶原的二次谐波发生 (SHG) 成像。在每个压力步骤确定 RLN 胶原纤维的笛卡尔应变张量、主应变 (Eps1) 和主方向。与仔猪的同一节段相比，第一主应变的值显着更大（p = 0.001，猪 = 0.0287 [IQR = 0.0161 – 0.0428]，仔猪 = 0.0061 [IQR = 0.0033 – 0.0156]）。此外，与仔猪相比，第二次压力增量的中位横向应变 Eyy ）在猪的右近端更大（p < 0.001，猪 = 0.0122 [IQR = 0.0033 – 0.0171]，仔猪 = 0.0013 [IQR = 0.00001 – 0.0 028]）。猪的右近端 RLN 的 Eyy 值显着大于左近端 RLN，但仔猪则不然 (p < 0.001)。与仔猪相比，猪 RLN 的组织学分析表明，神经外膜和神经内膜胶原蛋白的轴向排列在压力作用下增加。这些发现支持这样的假设：在猪模型的发育过程中，左右 RLN 对压缩压力的生物力学反应从相似变为不同。对与年龄相关的特发性 UVP 发病相关的这些发现的进一步研究可能会阐明潜在的病因机制。
Damage to the recurrent laryngeal nerve (RLN) caused by supraphysiological compression or tension imposed by adjacent tissue structures, such as the aorta, may contribute to onset of idiopathic unilateral vocal fold paralysis (iUVP) resulting in difficulty speaking, breathing, and swallowing. We previously demonstrated in adolescent pigs that the right RLN epineurium exhibits uniform composition of adipose tissue, with larger quantities along its length within the neck region in contrast to the left RLN that shows greater collagen composition in the thoracic region and greater quantities of adipose tissue in the neck region. In contrast, the epineurium in piglets was primarily composed of collagen tissue that remained uniform along the length of the left and right RLNs. Tensile testing of the left and right RLN in piglets and pigs showed associated differences in strain by RLN side and segment by age. The goal of this study was to investigate how external hydrostatic compression of the RLN affects the nerve’s connective tissue and microstructure. RLN segments were harvested from the distal (cervical/neck) regions and proximal (subclavian for the right RLN, thoracic for the left RLN) regions from eight adolescent pigs and nine piglets. RLN segments were isolated and assessed under fluid compression to test hypotheses regarding epineurium composition and response to applied forces. Second harmonic generation (SHG) imaging of epineurial collagen was conducted at 0, 40, and 80 mmHg of compression. The cartesian strain tensor, principal strain (Eps1), and principal direction of the RLN collagen fibers were determined at each pressure step. Significantly larger values of the 1st principal strain occurred in the proximal segments of the pig left RLN when compared to the same segment in piglets (p = 0.001, pig = 0.0287 [IQR = 0.0161 – 0.0428], piglet = 0.0061 [IQR = 0.0033 – 0.0156]). Additionally, the median transverse strain Eyy ) for the second pressure increment was larger in the right proximal segment of pigs compared to piglets (p < 0.001, pig = 0.0122 [IQR = 0.0033 – 0.0171], piglet = 0.0013 [IQR = 0.00001 – 0.0 028]). Eyy values were significantly larger in the right proximal RLN versus the left proximal RLNs in pigs but not in piglets (p < 0.001). In contrast to piglets, histological analysis of pig RLN demonstrated increased axial alignment of epineurial and endoneurial collagen in response to compressive pressure. These findings support the hypothesis that the biomechanical response of the RLN to compressive pressure changed from being similar to being different between the right and left RLNs during development in the porcine model. Further investigation of these findings associated with age-related onset of idiopathic UVP may illuminate underlying etiologic mechanisms.