1 Shriners Hospitals Pediatric Research Center, Center for Neural Repair and Rehabilitation, Lewis Katz School of Medicine at Temple University, Philadelphia, Pennsylvania.
2 Department of Bioengineering, College of Engineering, Temple University, Philadelphia, Pennsylvania.
J Neurotrauma. 2019 Jun 15;36(12):1965-1973. doi: 10.1089/neu.2018.5894. Epub 2018 Dec 19.
Myelomeningocele (MMC) is a devastating congenital neural tube defect that results in the exposure of spinal cord to the intrauterine environment, leading to secondary spinal cord injury and severe impairment. Although the mechanisms underlying the secondary pathogenesis are clinically relevant, the exact cause of -acquired spinal cord damage remains unclear. The objective of this study was to determine whether the hyaluronic acid (HA) concentration in amniotic fluid (AF) in the retinoic acid-induced model of MMC is different from that in normal controls and whether these differences could have an impact on the viscosity of AF. Our data shows that the concentration of HA in AF samples from fetuses with MMC (MMC-AF) and normal control samples (Norm-AF) were not significantly different at embryonic day 18 (E18) and E20. Thereafter, the HA concentration significantly increased in Norm-AF but not in MMC-AF. Compared with Norm-AF, the concentration of HA in MMC-AF and the viscosity of MMC-AF were significantly lower at E21. Agarose gel electrophoresis confirmed a significant reduction in the HA level of MMC-AF compared with Norm-AF at E21. No HA-degrading activity was detected in MMC-AF. In summary, we identified a deficiency in the AF level of HA and the viscosity of AF in fetal rats with MMC. These data are discussed in relation to a potential role the reduction in the AF viscosity due to the low level of HA may play in the exacerbating effects of mechanical trauma on spinal cord damage at the MMC lesion site.
脊髓脊膜膨出(MMC)是一种破坏性的先天性神经管缺陷,导致脊髓暴露于子宫内环境中,导致继发性脊髓损伤和严重损伤。尽管继发性发病机制的机制在临床上具有相关性,但继发性脊髓损伤的确切原因仍不清楚。本研究的目的是确定在维甲酸诱导的 MMC 模型中,羊水(AF)中的透明质酸(HA)浓度是否与正常对照组不同,以及这些差异是否会对 AF 的粘度产生影响。我们的数据表明,在胚胎第 18 天(E18)和第 20 天,患有 MMC 的胎儿(MMC-AF)和正常对照组(Norm-AF)的 AF 样本中的 HA 浓度没有显着差异。此后,HA 浓度在 Norm-AF 中显着增加,但在 MMC-AF 中没有增加。与 Norm-AF 相比,MMC-AF 中的 HA 浓度和 MMC-AF 的粘度在 E21 时显着降低。琼脂糖凝胶电泳证实,与 Norm-AF 相比,MMC-AF 中的 HA 水平在 E21 时显着降低。在 MMC-AF 中未检测到 HA 降解活性。总之,我们在患有 MMC 的胎鼠中发现了 AF 中 HA 水平和 AF 粘度的缺乏。这些数据与由于 HA 水平低导致的 AF 粘度降低可能在机械创伤对 MMC 损伤部位脊髓损伤的加重作用中发挥的潜在作用有关。