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中耳生物膜与突发性耳聋——光镜和透射电镜研究

Middle ear biofilm and sudden deafness - a light and transmission electron microscopy study.

作者信息

Li Hao, Staxäng Karin, Ladak Hanif M, Agrawal Sumit, Rask-Andersen Helge

机构信息

Department of Surgical Sciences, Otorhinolaryngology and Head and Neck Surgery, Uppsala University, Uppsala, Sweden.

The Rudbeck TEM Laboratory, BioVis Platform, Uppsala University, Uppsala, Sweden.

出版信息

Front Neurol. 2024 Dec 13;15:1495893. doi: 10.3389/fneur.2024.1495893. eCollection 2024.

Abstract

BACKGROUND

There still exists controversy about whether the healthy human middle ear mucosa is sterile or if it may harbor a diverse microbiome. Considering the delicacy of the human round window membrane (RWM), different mechanisms may exist for avoiding inner ear pathogen invasion causing sensorineural deafness. We re-analyzed archival human RWMs using light and transmission electron microscopy after decalcification to determine if bacteria are present in clinically normal human middle ears. We also searched for the presence of inborn immune defensive mechanisms within the round window niche (RWN), as previously reported in non-human primate ears.

MATERIALS AND METHODS

Five round window niches, removed and directly fixed at transcochlear petroclival meningioma surgery, were re-investigated after ethical permission using light and transmission electron microscopy. The morphology of the RWM, including its bony attachment and pseudomembrane outline, was analyzed. Moreover, 64 human temporal bones were investigated using synchrotron phase-contrast imaging (SR-PCI) aiming to identify potentially "hidden" spaces, including the RWN potentially harboring infectious material.

RESULTS

Histologic evidence of free-living bacteria and biofilm was found in 40% of RWNs in seemingly "healthy" middle ears. The RWM in these ears was pathologically changed with repealed epithelial and intercellular junctional integrity. Putative membranous defense machinery consisted of a lymphatic drainage system together with free phagocytic cells seemingly serving to protect the inner ear from alleged pathogens. Synchrotron analyses showed that a pseudomembrane was present in the human round window niche (RWN) in 80% of the specimens, of which 20% were complete. In 3%, the RWN contained dense tissue or serous fluid plugs partly obstructing the RWN. Infralabyrinthic clefts and tympanomeningeal fissures (Hyrtl's fissure) were occasionally enclosed by delicate membranes near the round window. These may represent predilection sites for "hidden" infections potentially endangering inner ear function, particularly in connection with round window surgery.

CONCLUSION

Considering the fragility of the normal human RWM, we speculate that occult colonies of biofilm may be a factor in surgeries involving the RWM, sensorineural hearing loss, and hearing preservation/fibrosis following cochlear implantation, and more controversially in hidden perilymph leaks causing sudden deafness and labyrinthine pathology.

摘要

背景

关于健康人的中耳黏膜是无菌的还是可能含有多种微生物群,目前仍存在争议。考虑到人类圆窗膜(RWM)的脆弱性,可能存在不同的机制来避免内耳病原体入侵导致感音神经性耳聋。我们在脱钙后使用光学显微镜和透射电子显微镜重新分析存档的人类圆窗膜,以确定临床上正常的人类中耳中是否存在细菌。我们还在圆窗龛(RWN)内寻找先天性免疫防御机制的存在,正如之前在非人灵长类动物耳朵中所报道的那样。

材料与方法

在获得伦理许可后,使用光学显微镜和透射电子显微镜对在经耳蜗岩斜脑膜瘤手术中切除并直接固定的5个圆窗龛进行重新研究。分析了圆窗膜的形态,包括其骨质附着和假膜轮廓。此外,使用同步加速器相衬成像(SR-PCI)对64块人类颞骨进行了研究,旨在识别潜在的“隐藏”空间,包括可能藏有感染性物质的圆窗龛。

结果

在看似“健康”的中耳的40%的圆窗龛中发现了自由生活细菌和生物膜的组织学证据。这些耳朵中的圆窗膜发生了病理改变,上皮和细胞间连接完整性遭到破坏。假定的膜性防御机制由淋巴引流系统和游离吞噬细胞组成,似乎有助于保护内耳免受所谓病原体的侵害。同步加速器分析表明,80%的标本中人类圆窗龛(RWN)存在假膜,其中20%是完整的。在3%的标本中,圆窗龛含有致密组织或浆液性液栓,部分阻塞了圆窗龛。迷路下裂和鼓室脑膜裂(Hyrtl裂)偶尔在圆窗附近被精细的膜所包围。这些可能是潜在危及内耳功能的“隐藏”感染的好发部位,特别是与圆窗手术有关的情况。

结论

考虑到正常人类圆窗膜的脆弱性,我们推测生物膜的隐匿菌落可能是涉及圆窗膜的手术、感音神经性听力损失以及人工耳蜗植入后听力保留/纤维化的一个因素,更具争议的是,在导致突发性耳聋和迷路病变的隐匿性外淋巴瘘中也是一个因素。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f62b/11671351/7d2dbb5cb410/fneur-15-1495893-g001.jpg

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