Histology of the endolymphatic sac of the rat ear and its relationship to surrounding blood vessels: the "endolymphatic glomerulus"

Histologic and histochemical studies of the endolymphatic sac of full-term rat fetuses were undertaken to clarify the anatomy of the endolymphatic sac, and the mechanism of endolymph circulation and regulation. Hitherto undescribed structure enveloping the sac with blood vessels extending from the sigmoid sinus resembling the kidney glomerulus was seen. This endolymphatic "glomerulus" is believed to provide a means of active exchange of water and electrolytes between blood vessels and the endolymphatic sac.     

The vascular supply of the endolymphatic sac.

The vascular anatomy of the endolymphatic sac in guinea pigs was examined following intravascular injection of silicone rubber (Microfil). Methacrylate resin of low viscosity (Mercox) was used to obtain vascular corrosion casts for scanning electron microscopy, which allowed more accurate differentiation between arteries and veins. The extensive vascular system around the sac comprises both arteries and veins, as well as lymphatic vessels. The arterial supply is derived mainly from the posterior meningeal artery in the posterior cranial fossa. In some cases a small artery also leads to the sac from the posterior vestibular artery in the labyrinth (in 7 of the 35 animals investigated). It courses together with the vein of the vestibular aqueduct along the walls of the endolymphatic duct. The blood is drained over the intermediate portion of the endolymphatic sac, which becomes lodged in a rich meshwork of capillaries, venules, veins and a few small arteries. A few venous trunks from both sac walls fuse with the vein of the vestibular aqueduct, which drains blood from the vestibule to the sigmoid sinus. Scanning electron microscopy also revealed numerous anastomosing vessels within bone channels with adjacent bone marrow sinusoids, which also probably contribute to the vascular supply of the endolymphatic sac.     

Ischemia of the endolymphatic sac.

A decrease in vascular density in the endolymphatic sac was suspected as a factor in the pathogenesis of endolymphatic hydrops in Meniere's disease. The present study was undertaken to explore this possibility by cutting the posterior meningeal artery and the sigmoid sinus above and below the external aperture of the vestibular aqueduct or by incision of the dura adjacent to the sinus in 18 guinea pigs. The lesions in the sac were greater in the segmental ablation of the artery and sinus and were consistently associated with the development of endolymphatic hydrops. Among the lesions shown in the sac epithelia, the intermediate portion was most often and most severely affected with a decrease in rugose formation and a flattening of the tall epithelial cells or replacement of epithelial cells by squamous type cells. A high correlation between the lesions in the intermediate portion and occurrence of hydrops suggests that the intermediate portion plays a greater role in the pathogenesis of endolymphatic hydrops. The sac luminal precipitates known to be increased in human Meniere's cases were decreased or absent in this study, which suggests that the increased amount is unlikely to be the cause of endolymphatic hydrops. The evidence supports the hypothesis that these substances are secreted by the endolymphatic sac. The limited sensory cell lesions seen in the cochleae and saccules are likely to be due to a temporary vascular ischemia and endolymphatic hydrops.     

A potential portal flow in the inner ear

OBJECTIVES/HYPOTHESIS: The aim of the present study was to visualize the flow direction of blood in the extraosseous part of the vein of the vestibular aqueduct (VVA) and to explore the effect of an induced obstruction in the distal part of the VVA before it merges with the sigmoid sinus. The endolymphatic sac has been implicated as a potential endocrine gland, which venules drain to the VVA. A reversal of the direction of flow in the VVA toward the inner ear could, through vestibular arteriovenous anastomosis, cause portal circulation in the inner ear. STUDY DESIGN: The authors conducted an experimental animal study using in vivo fluorescence microscopy. RESULTS: Obstructing the distal part of the VVA just before it empties into the sigmoid sinus immediately reverses the flow of blood in the VVA toward the inner ear. CONCLUSIONS: After an obstruction of the VVA, the drained venous blood from the endolymphatic sac may enter a portal circulation in the inner ear, which could cause disturbances in the endolymph homeostasis and potentially symptoms as seen in Meniere disease.     

Position and variations in the position of the canal system in the temporal bone. I. The canals of the pars petrosa between the margo superior and the meatus acusticus internus

The canals of the temporal bone were measured on 103 objects at different levels. The distances (mean and extremes) were estimated as well as the width of the following: the facial canal, semicircular canals, vestibule, internal acoustic meatus, sigmoid sinus, superior bulb of the jugular vein, carotid canal, eustachian tube, perilymphatic and endolymphatic ducts and sac, glossopharyngeal nerve and mastoid cells.     

The vein of the vestibular aqueduct with potential pathologic perspectives.

HYPOTHESIS: Pathologic changes around the vein of the vestibular aqueduct (VVA) may cause obstruction to the flow of blood toward the sigmoid sinus. Furthermore, a distal obstruction of this vessel may be responsible for a development of a retrograde flow of blood with concomitant drainage of endolymphatic sac (ES) substances to the inner ear. BACKGROUND: The VVA is responsible for the venous drainage of the vestibular apparatus and endolymphatic duct and ES. Previous studies have linked the VVA to Ménière's disease. The aim of the present article was a 3-dimensional perspective study of the VVA with its adjacent anatomic structures. METHODS: In 14 rats, the VVA was examined by 3-dimensional reconstruction of 2-microm serial sections, corrosion cast technique, and scanning electron microscopy. RESULTS: From the external aperture of the vestibular aqueduct, the VVA is interposed between the ES and the operculum. Three to 4 collecting venules from the ES drain into the VVA. The VVA merges at an oblique angle with the sigmoid sinus. CONCLUSION: The VVA courses near the ES, operculum, and sigmoid sinus and is potentially vulnerable to expanding structures in the cranial posterior fossa. The possible role of the VVA for the function of the ES under normal and pathologic conditions is discussed.     

单纯内淋巴囊减压术治疗梅尼埃病的远期疗效

报告以单纯内淋巴囊减压术治疗梅尼埃病５８例中，经随访５－６．５年的３０例眩晕完全消失者２１例。表明单纯内淋巴囊闰坟术与内淋巴囊切开术或分流术的疗效近似而且引起严重并发症的机会较少。并对本手术的作用机理，操作要领及并发症的预防等进行讨论。     

Histological evidence of specialized microcirculation of the endolymphatic sac

Summary A specialized type of blood vessel is demonstrated within the dense soft tissue areas of the vestibular aqueduct and vascular channels of the surrounding bone, including the paravestibular canaliculus (PVC). The vessel wall is formed by the collagen-smooth muscle bundles of these areas. The lumen of these vessels is irregular, and segments appear to be closed by apposition of the bundles. The vessels are continuous with the capillaries of the endolymphatic sac. It is not clear whether they are on the venous side of the capillary system, or on the arterial side and might possibly be part of an arteriovenous anatomoses system. Their possible role in some cases of Meniere's disease must be considered.Supported by USPHS Grant NS-06606 from the National Institute of Neurological and Communicative Disorders and Stroke     

Endolymphatic sac morphology following long-term kanamycin intoxication

The well-known toxicity pattern of aminoglycoside antibiotics has been used with the aim to produce waste products in the inner ear. The endolymphatic sac was studied after daily intraperitoneal injection of 75 mg/kg kanamycin for 10 and 20 days to see whether or not the endolymphatic sac showed signs of increased phagocytic activity. The epithelium of the endolymphatic sac was reduced in height, the cells were swollen and extremely thin. The dark epithelial cells were outnumbering the light cells. The subepithelial tissue showed an edematous swelling containing few blood vessels, collagen fibrils and fibroblasts with an empty appearance. There were few wide lateral intercellular spaces and there were intraluminal free floating cells. There were, in all, no clear morphological signs of increased phagocytic activity in the epithelium of the endolymphatic sac.     

The development of the endolymphatic duct and sac. A light microscopical study

The development and maturation of the endolymphatic sac were studied in the CBA/CBA mouse. The otocyst is developed at gestational day 10 and the primitive endolymphatic sac is present as a large slit-like appendage at day 12 of gestation. At day 18 the endolymphatic sac is clearly detached from the rest of the otocyst, forming a true sac. The epithelial lining consists of only one layer of immature cells containing large vesicles. The endolymphatic sac is surrounded by a rich network of vessels. One day before birth, the epithelial lining is uneven and the first signs of differentiation into light and dark cells is visible. This situation is more pronounced 2 days post partum when the sac also seems to be filled with a stainable material. At day 6 post partum the otic capsule fuses around the sac, forming the vestibular aqueduct. At 14 days post partum the sac is mature, with clearly developed light and dark cells and widened lateral intercellular spaces, constituting the rugose epithelium. The lumen is filled with a stainable precipitate and a few free-floating cells.     

耳后注射异硫氰酸荧光素标记葡聚糖的可能转运途径

目的 探讨耳后注射异硫氰酸荧光素标记的葡聚糖(FITC-Dextran)进入内耳的可能途径.方法 以异硫氰酸荧光素标记的葡聚糖(分子量为3 000~5 000,20 μl)为示踪剂,将200只出生24 h内的昆明乳鼠随机分为耳后对照组[5 mg/ml的葡聚糖(Dextran)20 μl耳后注射]、耳后实验组(5 mg/ml的FITC-Dextran 20 μl 耳后注射)、肌注对照组(5 mg/ml的葡聚糖20 μl 肌肉注射)、肌注实验组(5 mg/ml FITC-Dextran 20 μl 肌肉注射),每组50只;于给药后0 min、5 min、15 min、30 min、1 h、3 h、5 h、7 h、12 h、24 h处死动物,取其头颅做冰冻切片,应用激光共聚焦成像技术观察分析荧光示踪剂在乙状窦、内淋巴囊及耳蜗的分布及强度变化,以实验组与相应对照组荧光强度比值为强度值.结果 肌注实验组乙状窦在给药后3 h、内淋巴囊及耳蜗在给药后12 h可检测到荧光强度轻度增高,其余各部位各时间点均未检测出明显荧光增强.耳后实验组耳后注射示踪剂后,乙状窦、内淋巴囊分别在给药后即刻、耳蜗在给药后30 min可观察到荧光信号,随后荧光强度随时间延长依次升高,乙状窦、内淋巴囊、耳蜗的荧光强度达峰值时间分别为给药后5~15、30、60 min,到12小时强度均再次小幅度升高.结论 药物在耳后注射较肌肉注射更易于进入内淋巴液,可能径路为:示踪剂首先通过局部循环和局部渗透至乙状窦内富集,随后通过乙状窦与内淋巴囊间的脉络关系进入内淋巴液,最终逆内淋巴浓度梯度作用于内耳.     

Endolymphatic sac drainage and steroid-instillation surgery (EDSS) for intractable Meniere's disease

Endolymphatic sac surgery is one of the most widely accepted techniques used to treat intractable Meniere's disease. To improve this surgery, we developed the following techniques: A simple mastoidectomy was used to expose the endolymphatic sac between the sigmoid sinus and inferior margin of the posterior semicircular canal. The sac was opened and filled with a mass of prednisolone. A bundle of absorbable gelatin films was then inserted into the sac lumen to expand it, followed by gelatin sponges dipped in a high concentration of dexamethasone. Long-term results (17-32 months) in 20 patients with intractable Meniere's disease treated with endolymphatic sac drainage and steroid-insertion surgery (EDSS) showed that definitive spells were completely controlled in 15 of 20 cases (75%); all reports of vertigo decreased; hearing improved in 12 of 20 cases (60%); and annoyance due to tinnitus decreased in 15 of 20 cases (75%). Steroids directly instilled into the endolymphatic cavity may thus be more effective with the diseased inner ear organs than those applied via any other route. Draining of endolymphatic fluid at the sac into the mastoid cavity also contributed to these satisfactory EDSS results.     

内淋巴囊的脉管分布

目的：通过对豚鼠内淋巴囊表面的脉管及其粘膜下层结构的研究,了解其对内耳功能的影响,方法：用碳素黑水加１０％甲醛进行左心室灌注,将豚鼠的颞骨标本用冬青油透明并进行显微检查及透射电镜检查。结果：内淋巴囊表面有非常丰富的血管网,而且与乙状窦有很密切的联系,内淋巴囊周围被毛细血管,微静脉,静脉和个别微动脉形成的一个细密的环状血管网所包绕。毛细血管周围有丰富的淋巴窦、毛细血管与淋巴窦构成一个完整、细密的网状     

豚鼠内淋巴管和内淋巴囊的扫描电镜观察

目的 探讨豚鼠内淋巴管和内淋巴囊的表面超微结构特点。方法 用扫描电子显微镜观察正常豚鼠内淋巴管和内淋巴囊的表面超微结构。结果 内淋巴管的管腔面光滑、平整，上皮细胞表面的微绒毛少且短。细胞间隐窝小而少。内淋巴囊近端部上皮细胞表面的微绒毛明显增多、变长，细胞间隐窝明显．偶尔可见细胞顶部的胞饮小泡。内淋巴囊的中间部腔面上皮突起，复合折叠形成褶皱，细胞间隐窝多而大，突向囊腔的细胞多，囊腔内充满细胞和细胞碎片。根据电子密度上皮细胞可分为亮细胞和暗细胞两型，其中暗细胞较多，两型细胞表面均有大量长的微绒毛。细胞顶部可见到较多的胞饮小泡。内淋巴囊远端部的结构与内淋巴管近似，腔面光滑，上皮褶皱小，无细胞间隐窝，上皮细胞以亮细胞为主，表面微绒毛少而短，几乎没有胞饮小泡。结论 内淋巴管及内淋巴囊各部分的结构存在明显的不同，各有特点，这种结构特点可能与其在内淋巴代谢中的不同作用有关。     

General effects of hyperosmolar agents on the endolymphatic sac

The effects of glycerol, urea and mannitol on the structure of the murine endolymphatic sac were investigated at various time intervals after their administration. Within 15 min after administration of glycerol and urea the lumen of the endolymphatic sac was partially collapsed and the density of its contents was increased. At the same time many light epithelial cells displayed abundant intracytoplasmic granules containing floccular and/or lamellar material. A similar type of material was observed in the lumen in close proximity to these cells. This suggested that macromolecular substances were secreted into the endolymphatic sac lumen from these cells. Mannitol induced similar changes, though less pronounced. It is proposed that the changes in the endolymphatic sac following systemic administration of hyperosmolar substances reflect an ability of the endolymphatic sac to compensate for endolymphatic volume and pressure changes caused by these agents.     

The development of endolymphatic hydrops following CMV inoculation of the endolymphatic sac

The effect of inoculation of cytomegalovirus (CMV) into the endolymphatic sac was examined in CMV-seronegative and seropositive animals. Seronegative animals developed hearing loss, infection in the epithelial cells of the endolymphatic sac and perisaccular connective tissue, and endolymphatic hydrops. Control animals inoculated with inactivated CMV showed no hearing loss, viral infection, or endolymphatic hydrops. Seropositive animals showed complete protection from hearing loss and viral infection, yet a monocytic infiltrate was seen surrounding the endolymphatic sac. Associated with this localized immune response was mild evidence of endolymphatic hydrops in 40% (2/5) of the animals. Control seropositive animals inoculated with inactivated CMV showed no hearing loss or morphological changes. CMV then, can infect cells of the endolymphatic sac resulting in hearing loss and endolymphatic hydrops. The immune response to CMV in seropositive animals is protective, but is associated with endolymphatic sac inflammation.     

Localization of megalin in rat vestibular dark cells and endolymphatic sac epithelial cells

CONCLUSION: Megalin immunoreactivity was observed in kidney proximal tubule cells, vestibular dark cells, and epithelial cells of the endolymphatic sac. Endocytic mechanisms appear to differ between the endolymphatic sac and proximal tubule cells. We speculate that megalin is secreted by a certain type of cell into the endolymphatic space, and is then absorbed from the endolymphatic space by another type of cell to maintain endolymphatic sac homeostasis. OBJECTIVES: We previously detected megalin immunoreactivity in the rat cochlear duct. Megalin may be involved in endocytosis in the vestibular organ and endolymphatic sac. To examine this possibility, we extended our immunocytochemical investigation to the rat inner ear cells with special attention to vestibular dark cells and endolymphatic sac. MATERIALS AND METHODS: We observed immunoreactivity of megalin under light and electron microscopy. The primary antibody was rabbit polyclonal antibody that had been raised against rat immunoaffinity-purified megalin. RESULTS: The luminal membrane and subapical area of dark cells in the semicircular canal were immunolabeled. The stainable substance in the endolymphatic space was strongly stained. The cytoplasm of epithelial cells was also stained in various patterns.     

The endolymphatic sac in the Mondini disorder

The endolymphatic sacs are described in temporal bone specimens from a 31-year-old man with bilateral Mondini disorder. The ducts and sacs are thin-walled, cyst-like structures with complete absence of loose vascular perisac tissue, and are directly apposed to the bone of the vestibular aqueduct. Histological evidence of severe bone erosion is present in these specimens and is most marked in the intermediate and distal portions of the vestibular aqueduct. It is also present in the foveal region of the posterior temporal bone surface underlying the sac. Erosion of the bony wall of the paravestibular canaliculus (PVC) is demonstrable, with incorporation of the vein of the PVC inside the margin of the widened vestibular aqueduct. These findings suggest a causal relationship between pressure within the endolymphatic duct and sac and erosion of the surrounding bone. The absence of endolymphatic hydrops of the cochlea and vestibular organs in the Mondini disorder contrast significantly with the endolymphatic hydrops seen in Meniere's disease.     

内淋巴囊和肾小管上皮细胞透明质酸合成酶mRNA的表达

目的 用寡聚核苷酸探针检测内淋巴囊和肾小管上皮细胞透明质酸合成酶mRNA表达的异同。方法 通过查阅核酸序列数据库,自行设计并合成了透明质酸合成酶寡聚核苷酸探针,应用原位杂交技术检测透明质酸合成酶mRNA在豚鼠内淋巴囊和肾小管上皮细胞的表达。结果 在内淋巴囊近侧端、中间部和肾小管部分上皮细胞胸浆显示透明质酸合成酶mRNA的阳性表达,但近曲小管的阳性细胞百分数稍多。结论 不但扩大了核酸杂交的应用范围,还为内淋巴囊和肾小管上皮细胞对水电解质平衡可能都具有透明质酸／透明质酸酶的双重调节作用提供了理论依据。     

Effects of amiloride on the endolymphatic sac

The effect of amiloride on the murine endolymphatic sac was investigated. The amiloride caused collapse of the lateral intercellular spaces in the endolymphatic sac epithelium and a subsequent mild endolymphatic hydrops. These changes indicated a decreased absorption of endolymph in the endolymphatic sac. Amiloride is known to inhibit the transcellular fluid transport without inducing any changes in the paracellular fluid transport. It is therefore suggested that amiloride specially inhibits the fluid and ion exchange in the apical portion of the epithelial cells resulting a decrease in transcellular fluid transport across the endolymphatic sac epithelium. The transcellular fluid transport seems to be one of the main mechanisms in the endolymphatic sac fluid exchange system.