Spinal Cord Contusion Causes Acute Plasma Membrane Damage
Spinal Cord Contusion Causes Acute Plasma Membrane Damage
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DOI：
10.1089/neu.2008.0523
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发表时间：
2009-04-01
影响因子：
4.2
通讯作者：
LaPlaca, Michelle C.
中科院分区：
文献类型：
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作者：
Simon, Crystal M.;Sharif, Shan;LaPlaca, Michelle C.
脊髓损伤 (SCI) 会引发一系列复杂的事件，导致进行性损伤和功能丧失。由于机械冲击而导致质膜完整性受损是一种急性事件，可能导致细胞功能障碍。因此，本研究的目的是更好地了解与 SCI 相关的急性质膜损伤程度，作为损伤严重程度和膜缺陷大小的函数。在挫伤之前，将细胞不渗透的荧光染料注射到成年雄性大鼠的脑脊液中，并对 SCI 后 10 分钟内吸收染料的细胞体和轴突的解剖位置进行量化。荧光黄的吸收被评估为冲击力的函数（实验组：假手术、100 kdyn、150 kdyn 和 200 kdyn 力）。在另一组动物中，使用不同大小的 FITC 缀合葡聚糖分子（半径分别为 1.6 nm 和 2.7 nm 的 3 kDa 和 10 kDa）来估算中度损伤（150 kdyn 力）后膜缺陷的大小。定量显示，细胞对荧光黄的摄取与机械冲击力呈正相关，表明损伤的严重程度与急性膜衰竭的程度有关。此外，在中度损伤后，与假手术对照组相比，细胞体和轴突（分别距离震中 2 毫米和 3 毫米）吸收了显着更多的 3-kDa 和 10-kDa 葡聚糖通透性标记。可渗透的神经元细胞体表现出以细胞周起泡为特征的形态学外观，表明质膜受损与病理生理学细胞改变有关。总的来说，这些结果增强了我们对急性 SCI 的理解，并为开发新的治疗策略提供了目标。
Spinal cord injury (SCI) launches a complex cascade of events that leads to progressive damage and loss of function. Compromise of plasma membrane integrity due to the mechanical impact is an acute event that may contribute to cellular dysfunction. Therefore, the objective of this study was to better understand the extent of acute plasma membrane damage associated with SCI as a function of injury severity and membrane defect size. Fluorescent cell-impermeant dyes were injected into the cerebrospinal fluid of adult male rats prior to contusion injury, and the anatomical location of cell bodies and axons taking up the dye within 10 min following SCI was quantified. Lucifer yellow uptake was assessed as a function of impact force (experimental groups: sham, 100 kdyn, 150 kdyn, and 200 kdyn force). In a separate group of animals, FITC-conjugated dextran molecules of various sizes (3 kDa and 10 kDa with a 1.6-nm and 2.7-nm radius, respectively) were used to approximate the size of membrane defects following moderate injury (150 kdyn force). Quantification revealed that cellular uptake of lucifer yellow was positively correlated with the force of the mechanical impact, indicating that the severity of injury is related to the degree of acute membrane failure. In addition, after moderate injury, cell bodies and axons (located up to 2 mm and 3 mm from the epicenter, respectively) took up significantly more of the 3-kDa and 10-kDa dextran permeability marker compared to sham controls. Permeable neuronal cell bodies exhibited a morphological appearance characterized by pericellular blebbing, suggesting that plasma membrane compromise is associated with pathophysiological cellular alterations. Collectively, these results enhance our understanding of acute SCI and provide targets for developing novel treatment strategies.