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The maculae sacculi and utriculi of the chinchilla vestibular labyrinth have been studied by freeze-fracture method. In the replicas extensive zonulae occludentes have been found between sensory and supporting cells at the endolymphatic surface. Gap junctions are located between the supporting cells. Some intramembranous specializations of the synaptic regions are described in both types of the sensory cells.
Radioautographic studies were conducted on early developmental stages of the inner ear in monkey (Macaca mulatta) embryos ranging in age from stage 11 to stage 20 (25 to 39 days' gestation) and labeled for one hour with [3H] thymidine. The most active period of proliferation occurred at stage 13, at which time all regions of the otocyst, including the endolymphatic duct, were heavily labeled. In subsequent stages the dorsal portion of the endolymphatic duct failed to incorporate label, whereas proliferation continued in the ventral portion of the duct near its communication with the medial wall of the otocyst. The duct thus appeared to grow upward as a result of cell division from below. Mitotic activity continued in the remainder of the otocyst although there was a progressive temporal decrease in the labeling index. Spatial gradients also occurred, with dorsal and lateral regions less active than ventral and medial ones. As the otocyst differentiated, the cells in various areas became attenuated. These flattened cells were still capable of undergoing cell division, as indicated by the presence of labeled nuclei in all regions of the utricle, saccule, semicircular ducts, and cochlear duct.
Occlusion of the anterior vestibular artery has resulted in severe degeneration and new bone formation limited to the utricle, saccule, and superior and lateral semicircular canals. Depriving the inner ear of its main blood supply, i.e. the internal auditory artery, has resulted in severe degeneration and ossification of the entire membranous labyrinth, except the endolymphatic duct and sac. A more severe cochlear sclerosis was seen when both arterial and venous blood supplies to the cochlea were occluded. The implications of these findings on the etiology and management of inner ear disorders are emphasized.
Little is known about the origin or the metabolism of otoconia. Streptomycin sulfate was found to cause a decrease in their number on the otolithic membrane of the utricle and saccule in guinea pigs. The remaining otoconia on the otolithic membrane varied in shape and size and giant otoconia with multilayered arrangement were observed by means of a scanning electron microscope. These otoconia contained the normal amount of calcium in the form of standard calcium calcite crystal. The lost otoconia were found attached to the surface of some vestibular dark cells. Otoconia in this new position were irregular, shrunken or fragmented. Their calcium content, measured with an X-ray micro-analyzer, was variably diminished. The dark cells appeared to be actively engaged in absorption of calcium ions, from the attached otoconia. The dark cell is considered to be a receptacle for the disposal of otoconia.
Temporal bone specimens were obtained at autopsy from a six-week-old victim of sudden infant death syndrome. The inner ears were microdissected and studied by a combination of light and scanning electron microscopy. Otoconia were completely absent from the sensory organs of the saccule and utricle on both sides. However, the gelatinous otoconial membranes, neuroepithelia, and innervation were normal. In parallel with unusually light pigmentation of the skin in this Negro infant, relatively few melanocytes were found in the membranous walls of the saccule and utricle. No abnormalities were present in other inner ear structures. This anomaly, which we believe was congenital in nature, is strikingly similar to a genetically determined inner ear defect which has been extensively studied in experimental animals.
The effect of tissue preparation on calcium and potassium weight percent in the otoconial layer in the utricle and saccule was studied in four groups of OF1 mice with electron probe X-ray microanalysis. Glutaraldehyde and freeze-drying, glutaraldehyde and air-drying, air-drying, and cryo-fixation and freeze-drying were compared. Ca and K changed significantly in the utricle depending on the method used (P < 0.001), and K changed significantly in the saccule (P < 0.001). We chose cryo-fixation with freeze-drying for the quantitative analysis of the otolithic membrane because this method provided the highest values of Ca and K with minimum loss of Ca and K. Microcrystalline salt standards mounted on scanning electron microscopy holders were used for the quantification of Ca and K by the peak-to-local-background (P/B) ratio method. The P/B ratio in standards with reproducible results, when plotted against weight percent, gave a straight line for Ca (r = 0.99, P < 0.001) and K (r = 0.98, P < 0.001). The Ca and K weight percent in otoconia showed similar frequency distributions in the utricle and saccule.
Temporal bone studies in an adult with a moderately severe, bilateral sensorineural hearing loss revealed bilateral cochlear changes 13 years after mumps infection. The organ of Corti was completely absent in the greater part of the superior horizontal basal limbs, with occasional hair cell loss throughout the rest of the cochlea. The outer sulcus cell area was degenerated. The stria vascularis was normal, as was the tectorial membrane, except for small hyaline droplets. The number of nerve fibers was extremely decreased in the spiral bony lamina of the basal turns. Basophilic material, possibily representing degeneration of otoliths, was present in the saccule and utricle, bilaterally, with small amounts in all of the ampullae. This was considered to be either a possible result of cytotoxic cancerocidal therapy, or an incidental nonspecific change.
1. The endolymphatic system is morphologically a close system. The inner surface of the wall is tightly lined with an epithelium of ectodermal origin. The perilymphatic spaces are enlarged intercellular spaces which are built from the embryonic mesenchyme. 2. The perilymph ist an ultrafiltrate of plasma. There is probably a flow from the cerebrospinal fluid which is constantly renewed. The diffusion in the perilymph is dependent on the concentration and the size of the molecules. The endolymph is mainly a perilymph-filtrate. The "secretory" epithelia (e.g. stria vascularis cells and other tissues) of the endolymphatic system perform an important role to sustain the potassium and sodium concentrations. The ionic concentrations regulate the water movement also the volume of the endolymphatic spaces. They are maintained by anoxy-sensitive pumps. 3. The DC potential within the endolymphatic spaces represents the movement of certain electrical charge through membranes. By applying various inhibitors it is possible to distinguish the pumping mechanisms, and to observe the continuous changes of potassium and sodium concentrations with Na+ specific electrodes and K+ specific electrodes. There are probably three interdependent sources of driving-forces: a. A positively electrogenic K+-pump which is anoxia-sensitive and can be inhibited by Ethacrynic acid. This mechanism is more active in stria cells and less so in utricle and saccule. b. A negatively electrogenic Na+-K+ exchange-pump in all parts of the endolymphatic spaces is inhibited by Ouabain or anoxia. c. The passive diffusion of potassium-ions from endolymph to perilymph results an electro-negative effect.
The distribution of tyrosine hydroxylase (TH)-like immunofluorescence was analyzed in the guinea pig vestibular ganglia and end organs using a monoclonal antibody to TH. TH was chosen as a marker for the sympathetic fibers because TH regulates the first step of catecholamine synthesis by converting tyrosine to dopa. In the vestibular ganglia, there were TH-positive nerve fibers having distinct varicosities surrounding the vestibular ganglion cells. In the sensory areas, there was a sympathetic plexus in the subepithelial tissue of the saccule, the utricle, and the crista ampullaris. We speculated that the sympathetic innervation has a direct influence on the vestibular ganglion cells and diffuse influence on the capillary permeability.
This study examined the additive effects of two mutant genes, pallid (pa) and tilted head (th), on otolith formation in mice. Four strains of mice were bred: (1) a control strain, heterozygous for both pa and th. (2) a pallid strain, homozygous for pa, (3) a tilted head strain, homozygous for th, and (4) a double mutant strain, homozygous for both pa and th. The results were confirmed (1) behaviorally, by the animals' ability to swim, and (2) by histological examination of the inner ear. The findings suggest significant differences in mean otolith scores between all possible pairs of strains. As expected, the controls had normal otoliths and the pa/th strain the most severe otolith defects. Furthermore, there was a significant directional asymmetry in mean otolith scores between the utricle and saccule of the R and L ears for both pa and th strains. The results also showed a highly significant linear relationship between poor swimming ability and reduction of otoconia (r = 0.94, F = 92.14, p less than .001).
Described in the foregoing are postoperative changes in the ductus reuniens and the utriculo-endolymphatic valve of the membranous labyrinth of the inner ear upon obstruction of the endolymphatic duct in normal guinea-pigs. The ductus reuniens was postoperatively dilated more than three times that of the normal ear, and dilated to a maximum degree within the first 12 hours. The utriculo-endolymphatic valve was found to be open two days after the operation, and there was a tendency for the number of animals with an open valve to increase with time. At three weeks and also at two months after the operation, there were some animals whose utricles were compressed by the dilated saccules, and as a result, their utricular ducts and utriculo-endolymphatic valves appeared narrowed.
Long-duration exposure to microgravity disrupts human balance and spatial orientation, yet the molecular mechanisms underlying vestibular adaptation to spaceflight remain poorly understood. Here, we tested the hypothesis that the saccule, the primary gravity-sensing otolith organ, undergoes selective remodeling during spaceflight and contributes to transient postflight postural instability. Using a cross-species approach, we combined transcriptomic analysis of mouse otolith organs with physiological assessments in astronauts. Laser microdissection-based RNA sequencing of mouse otolith sensory epithelia after a 35-d spaceflight revealed pronounced, organ-specific transcriptomic remodeling in the saccule, whereas the utricle remained stable. Principal component and clustering analyses demonstrated that the saccular transcriptome shifted toward an utricle-like profile under microgravity, accompanied by changes in genes related to synaptic and neuronal function. Promoter motif analysis identified NFAT-associated transcriptional networks, suggesting Ca2+-dependent regulation of synaptic plasticity as a potential molecular substrate of gravity-dependent adaptation. In parallel, vestibular testing in astronauts following long-duration missions (157 to 328 d) revealed selective attenuation of saccule-mediated cervical vestibular-evoked myogenic potentials and increased postural sway immediately after return to Earth, while utricle-mediated responses and semicircular canal function were preserved. Both saccular function and postural stability recovered within approximately 10 d. Notably, early postflight postural instability was partially mitigated by noisy galvanic vestibular stimulation, consistent with stochastic resonance-mediated sensory enhancement. Together, these findings identify the saccule as a plastic gravity sensor and establish a mechanistic link between peripheral molecular remodeling and functional balance deficits after spaceflight, providing a framework for developing countermeasures to facilitate vestibular readaptation during human space exploration.
Specimens of human otoconia obtained from autopsy material and representing various stages from fetal to advanced old age, were studied by microdissection, scanning electron microscopy, electron microprobe analysis, and x-ray powder diffraction. The typical adult otoconial configuration is a cylindrical, finely serrated body with pointed ends; crystallographically, it corresponds to a single crystal of calcite. Other, less numerous typed include jointed otoconia, pure rhombohedrons and multifaceted, presumably immature forms. Many otoconia achieve the adult configuration during fetal development. The multifaceted otoconia are most numerous, and the rhombohedrons proliferate, during childhon in the young adult, but saccular otoconia are the larger. In middle and advanced age the otoconia decrease in number, especially in the saccule. Saccular otoconia degenerate progressively in a posteroanterior direction across the macula; they assume a specific, fibours, hollowed-out appearance, which is not duplicated by either chemical etching or autolysis. Neogenesis and growth of otoconia appear to occur postnatally, with different characteristic growth potentials for those of the saccule and the utricle. Age-related saccular otoconial degeneration appears to involve the organic material, which disappears either before or simultaneously with the mineral substance.
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A brief illustrated atlas demonstrates the progressive relationships of the anatomical structures of the cat's middle ear as one dissects these from the attic approach. There was an attempt to demonstrate the nerves of the lateral semicircular canal and the utricle but without preserving the footplate of the stapes to afford an unobstructed view of the nerves. For the first time, the anatomical features of the cat's middle are are brought together in a progressively illustrated and single source.
Ocular accomodation was measured in human subjects while they were rotated at 1 degree/sec about their naso-occipital axes. Sixteen normal subjects were tested with 45 complete and 27 partial revolutions. Naso-occipital rotations ipsilateral to the eye being observed caused accommodative, lens-thickening changes. This effect begin at about 14 degrees from head upright position, tended to reach a maximum by 45 degrees and usually stayed at this level until about 90 degrees. The values tended to return to control level by 180 degrees. With naso-occipital roll in the direction opposite to the eye being observed, there was little change until about 135 degrees at which point further roll was typically clear accomodation. This continued to a maximum at about 270 degrees rotation, and at about 350 degrees returned to control values. Arguments are presented relating this response to the utricles, which are approximately parallel to earth horizontal. The threshold of this response, between 3.7 and 77 cm/sec2, is similar to the threshold of linear acceleration when measured by other means.
This investigation of the vestibular apparatus of rats exposed for 20 days to weightlessness on board an earth satellite and to acceleration during take-off and landing has revealed a set of changes in the structural and functional organization, such as adjoinment of the otolith to the utricle receptor surface and peripheral localization of the nucleoli inside the receptor cells' nuclei. Destruction of some receptor cells, apparently due to increased swelling of the vestibular apparatus tissue and alteration of the shape and structure of the otoconia were observed. In the horizontal crista, detachment of the cupula took place.
The vein of the vestibular aqueduct (VVA) was investigated in a series of 40 human temporal bones. The processing included vascular injection with a colored medium, decalcification and cutting in serial, thick sections, which were put in a clear fluid and studied with a stereo-microscope. The labyrinthine roots of the VVA are the single veins of the ampulla and simple limbs of the semicircular canals and of the posterior wall of the utricle. They drain the rich capillary bed of the simple endolymphatic walls of the canals and the utricle, as well as a small peripheral area of the cristae and the utricular macula. The VVA leaves the vestibule through an individual bone canal running parallel to the vestibular aqueduct up to the dura of the posterior side of the petrosa in the area of the endolymphatic sac. It then opens in the inferior petrosal sinus or the jugular bulb. The vein receives other branches from the bone, dura and sac. Correct information on the course of this vein appears to be lacking in contemporary textbooks and articles, although it has been correctly described since the last century.