Department of Otolaryngology-Head and Neck Surgery, Medical University of South Carolina, Charleston, South Carolina 29425, USA.
Otolaryngol Head Neck Surg. 2011 Dec;145(6):1007-15. doi: 10.1177/0194599811416778. Epub 2011 Sep 23.
The degeneration of hair cells and spiral ganglion neurons (SGNs) is an important pathologic process in the development of sensorineural hearing loss. In a murine model, predictable and reproducible damage to SGNs occurs through the application of ouabain to the round window. Recent evidence has shown that the chemokine stromal cell-derived factor-1 (SDF-1) is a potent chemoattractant of hematopoietic stem cells (HSCs) and provides trophic support to injured tissues during development and maturation. The hypothesis for the current study is that expression of SDF-1 plays an important role in protecting SGNs and preventing further degeneration in the setting of cochlear injury.
Prospective, controlled.
Academic research laboratory.
Auditory brainstem response (ABR) and the expression of SDF-1 mRNA and protein were examined 1, 3, 7, 14, and 30 days after application of ouabain in 35 adult mice.
Following ouabain application, real-time reverse-transcription polymerase chain reaction for SDF demonstrates increased mRNA expression following ouabain injury in nontransplanted mice. A significant increase in SDF protein expression was also observed using immunolabeling techniques and Western blot analysis.
SDF-1 expression is increased in the auditory nerve following cochlear injury. Further knowledge about the cochlear microenvironment, including SDF-1, is critical to maximizing HSC engraftment in the injured cochlea and providing a therapeutic option for sensorineural hearing loss.
毛细胞和螺旋神经节神经元(SGN)的变性是感音神经性听力损失发展过程中的一个重要病理过程。在小鼠模型中,通过向圆窗应用哇巴因可预测和重现 SGN 的损伤。最近的证据表明,趋化因子基质细胞衍生因子-1(SDF-1)是造血干细胞(HSC)的有效趋化因子,并在发育和成熟过程中为受损组织提供营养支持。目前研究的假设是,SDF-1 的表达在保护 SGN 免受耳蜗损伤和防止进一步变性方面发挥重要作用。
前瞻性、对照。
学术研究实验室。
在 35 只成年小鼠中,在应用哇巴因后 1、3、7、14 和 30 天,通过听觉脑干反应(ABR)和 SDF-1 mRNA 和蛋白的表达进行检查。
哇巴因损伤后,通过实时逆转录聚合酶链反应检测 SDF,非移植小鼠的 SDF 表达增加。免疫标记技术和 Western blot 分析也观察到 SDF 蛋白表达的显著增加。
耳蜗损伤后听神经中 SDF-1 的表达增加。进一步了解耳蜗微环境,包括 SDF-1,对于最大限度地提高 HSC 在受损耳蜗中的植入率并为感音神经性听力损失提供治疗选择至关重要。