scholarly journals Toxic Effects of 3,3′-Iminodipropionitrile on Vestibular System in Adult C57BL/6J Mice In Vivo

2020 ◽  
Vol 2020 ◽  
pp. 1-11
Author(s):  
Shan Zeng ◽  
Wenli Ni ◽  
Hui Jiang ◽  
Dan You ◽  
Jinghan Wang ◽  
...  
Keyword(s):  
Inner Ear ◽  
Vestibular System ◽  
Vestibular Function ◽  
Cell Loss ◽  
Supporting Cell ◽  
Sensory Epithelium ◽  
Toxic Effects ◽  
Ocular Reflex ◽  
Vestibular Ocular Reflex

The utricle is one of the five sensory organs in the mammalian vestibular system, and while the utricle has a limited ability to repair itself, this is not sufficient for the recovery of vestibular function after hair cell (HC) loss induced by ototoxic drugs. In order to further explore the possible self-recovery mechanism of the adult mouse vestibular system, we established a reliable utricle epithelium injury model for studying the regeneration of HCs and examined the toxic effects of 3,3′-iminodiproprionitrile (IDPN) on the utricle in vivo in C57BL/6J mice, which is one of the most commonly used strains in inner ear research. This work focused on the epithelial cell loss, vestibular dysfunction, and spontaneous cell regeneration after IDPN administration. HC loss and supporting cell (SC) loss after IDPN treatment was dose-dependent and resulted in dysfunction of the vestibular system, as indicated by the swim test and the rotating vestibular ocular reflex (VOR) test. EdU-positive SCs were observed only in severely injured utricles wherein above 47% SCs were dead. No EdU-positive HCs were observed in either control or injured utricles. RT-qPCR showed transient upregulation of Hes5 and Hey1 and fluctuating upregulation of Axin2 and β-catenin after IDPN administration. We conclude that a single intraperitoneal injection of IDPN is a practical way to establish an injured utricle model in adult C57BL/6J mice in vivo. We observed activation of Notch and Wnt signaling during the limited spontaneous HC regeneration after vestibular sensory epithelium damage, and such signaling might act as the promoting factors for tissue self-repair in the inner ear.

scholarly journals Vestibular agnosia in traumatic brain injury and its link to imbalance

Brain ◽  
2020 ◽  
Author(s):  
Elena Calzolari ◽  
Mariya Chepisheva ◽  
Rebecca M Smith ◽  
Mohammad Mahmud ◽  
Peter J Hellyer ◽  
...  
Keyword(s):  
Traumatic Brain Injury ◽  
Brain Injury ◽  
Inner Ear ◽  
Temporal Lobe ◽  
Vestibular Function ◽  
Ocular Reflex ◽  
Vestibular Ocular Reflex ◽  
Inferior Longitudinal Fasciculus ◽  
The Right ◽  
Acute Patients

Abstract Vestibular dysfunction, causing dizziness and imbalance, is a common yet poorly understood feature in patients with TBI. Damage to the inner ear, nerve, brainstem, cerebellum and cerebral hemispheres may all affect vestibular functioning, hence, a multi-level assessment—from reflex to perception—is required. In a previous report, postural instability was the commonest neurological feature in ambulating acute patients with TBI. During ward assessment, we also frequently observe a loss of vertigo sensation in patients with acute TBI, common inner ear conditions and a related vigorous vestibular-ocular reflex nystagmus, suggesting a ‘vestibular agnosia’. Patients with vestibular agnosia were also more unbalanced; however, the link between vestibular agnosia and imbalance was confounded by the presence of inner ear conditions. We investigated the brain mechanisms of imbalance in acute TBI, its link with vestibular agnosia, and potential clinical impact, by prospective laboratory assessment of vestibular function, from reflex to perception, in patients with preserved peripheral vestibular function. Assessment included: vestibular reflex function, vestibular perception by participants’ report of their passive yaw rotations in the dark, objective balance via posturography, subjective symptoms via questionnaires, and structural neuroimaging. We prospectively screened 918 acute admissions, assessed 146 and recruited 37. Compared to 37 matched controls, patients showed elevated vestibular-perceptual thresholds (patients 12.92°/s versus 3.87°/s) but normal vestibular-ocular reflex thresholds (patients 2.52°/s versus 1.78°/s). Patients with elevated vestibular-perceptual thresholds [3 standard deviations (SD) above controls’ average], were designated as having vestibular agnosia, and displayed worse posturography than non-vestibular-agnosia patients, despite no difference in vestibular symptom scores. Only in patients with impaired postural control (3 SD above controls’ mean), whole brain diffusion tensor voxel-wise analysis showed elevated mean diffusivity (and trend lower fractional anisotropy) in the inferior longitudinal fasciculus in the right temporal lobe that correlated with vestibular agnosia severity. Thus, impaired balance and vestibular agnosia are co-localized to the inferior longitudinal fasciculus in the right temporal lobe. Finally, a clinical audit showed a sevenfold reduction in clinician recognition of a common peripheral vestibular condition (benign paroxysmal positional vertigo) in acute patients with clinically apparent vestibular agnosia. That vestibular agnosia patients show worse balance, but without increased dizziness symptoms, explains why clinicians may miss treatable vestibular diagnoses in these patients. In conclusion, vestibular agnosia mediates imbalance in traumatic brain injury both directly via white matter tract damage in the right temporal lobe, and indirectly via reduced clinical recognition of common, treatable vestibular diagnoses.

Requirement for Brn-3c in maturation and survival, but not in fate determination of inner ear hair cells

Development ◽  
1998 ◽  
Vol 125 (20) ◽  
pp. 3935-3946 ◽  
Author(s):  
M. Xiang ◽  
W.Q. Gao ◽  
T. Hasson ◽  
J.J. Shin
Keyword(s):  
Hair Cell ◽  
Inner Ear ◽  
Hair Cells ◽  
Cell Loss ◽  
Supporting Cell ◽  
Sensory Epithelium ◽  
Cell Phenotype ◽  
Sensory Epithelia ◽  
Vestibular Sensory Epithelia ◽  
And Migration

Mutations in the POU domain gene Brn-3c causes hearing impairment in both the human and mouse as a result of inner ear hair cell loss. We show here that during murine embryogenesis, Brn-3c is expressed in postmitotic cells committed to hair cell phenotype but not in mitotic progenitors in the inner ear sensory epithelium. In developing auditory and vestibular sensory epithelia of Brn-3c−/− mice, hair cells are found to be generated and undergo initial differentiation as indicated by their morphology, laminar position and expression of hair cell markers, including myosins VI and VIIa, calretinin and parvalbumin. However, a small number of hair cells are anomalously retained in the supporting cell layer in the vestibular sensory epithelia. Furthermore, the initially differentiated hair cells fail to form stereociliary bundles and degenerate by apoptosis in the Brn-3c−/− mice. These data indicate a crucial role for Brn-3c in maturation, survival and migration of hair cells, but not in proliferation or commitment of hair cell progenitors.

scholarly journals Finding a Balance: A Systematic Review of the Biomechanical Effects of Vestibular Prostheses on Stability in Humans

2020 ◽  
Vol 5 (2) ◽  
pp. 23
Author(s):  
Felix Haxby ◽  
Mohammad Akrami ◽  
Reza Zamani
Keyword(s):  
Vestibular System ◽  
Postural Sway ◽  
Vestibular Function ◽  
Vestibular Stimulation ◽  
Significant Heterogeneity ◽  
Vestibular Loss ◽  
Ocular Reflex ◽  
Gait Characteristics ◽  
Vestibulo Ocular Reflex ◽  
Meta Analyses

The vestibular system is located in the inner ear and is responsible for maintaining balance in humans. Bilateral vestibular dysfunction (BVD) is a disorder that adversely affects vestibular function. This results in symptoms such as postural imbalance and vertigo, increasing the incidence of falls and worsening quality of life. Current therapeutic options are often ineffective, with a focus on symptom management. Artificial stimulation of the vestibular system, via a vestibular prosthesis, is a technique being explored to restore vestibular function. This review systematically searched for literature that reported the effect of artificial vestibular stimulation on human behaviours related to balance, using the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) technique. A total of 21 papers matched the inclusion criteria of the literature search conducted using the PubMed and Web of Science databases (February 2019). The populations for these studies included both healthy adults and patients with BVD. In every paper, artificial vestibular stimulation caused an improvement in certain behaviours related to balance, although the extent of the effect varied greatly. Various behaviours were measured such as the vestibulo-ocular reflex, postural sway and certain gait characteristics. Two classes of prosthesis were evaluated and both showed a significant improvement in at least one aspect of balance-related behaviour in every paper included. No adverse effects were reported for prostheses using noisy galvanic vestibular stimulation, however, prosthetic implantation sometimes caused hearing or vestibular loss. Significant heterogeneity in methodology, study population and disease aetiology were observed. The present study confirms the feasibility of vestibular implants in humans for restoring balance in controlled conditions, but more research needs to be conducted to determine their effects on balance in non-clinical settings.

scholarly journals SYSTEMIC KANAMYCIN TREATMENT HAS NO EFFECT ON CELL NUMBERS IN THE MOUSE UTRICULAR MACULA

2011 ◽  
Vol 24 (2) ◽  
pp. 69 ◽  
Author(s):  
Mette Kirkegaard ◽  
Stig Å Severinsen ◽  
Lise Wogensen ◽  
Jens R Nyengaard
Keyword(s):  
Hair Cell ◽  
Hair Cells ◽  
Caspase 3 ◽  
Cell Loss ◽  
Supporting Cell ◽  
Cell Number ◽  
Sensory Epithelium ◽  
Positive Staining ◽  
Survival Times ◽  
Cell Numbers

The aim of the present study is to estimate the total number of the sensory hair cells (chalice innervated and bouton innervated) and supporting cells in the mouse utricular sensory epithelium at two different time points after systemic kanamycin treatment. Mice were given two daily subcutaneous injections of kanamycin (600 or 900 mg/kg) for 15 consecutive days and allowed to survive either 1 or 3 weeks after end of treatment. Cell numbers were estimated using a physical fractionator. Paraffin-embedded tissue was immunohistochemically stained for active caspase-3 in order to detect apoptosis. There was no change in hair cell or supporting cell number after treatment with kanamycin and the survival time had no effect. Although no positive staining for caspase-3 was seen, hair cells with swollen chalices and dark stained nuclei were observed in the sensory epithelium of the treated animals, indicating some effect of the treatment. In conclusion, the dosing regime and survival times studied here are not sufficient to induce hair cell loss in the mouse utricle.

scholarly journals Prenatal electroporation-mediated gene transfer restores Slc26a4 knock-out mouse hearing and vestibular function

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Hiroki Takeda ◽  
Toru Miwa ◽  
Min Young Kim ◽  
Byung Yoon Choi ◽  
Yorihisa Orita ◽  
...  
Keyword(s):  
Survival Rate ◽  
Gene Transfer ◽  
Inner Ear ◽  
Morphological Changes ◽  
Treatment Strategies ◽  
Vestibular Function ◽  
Knock Out ◽  
Genetic Hearing Loss ◽  
Mouse Hearing

AbstractThe otocyst, an anlage of the inner ear, presents an attractive target to study treatment strategies for genetic hearing loss and inner ear development. We have previously reported that electroporation-mediated transuterine gene transfer of Connexin30, utilizing a monophasic pulse into Connexin30−/− mouse otocysts at embryonic day 11.5, is able to prevent putative hearing deterioration. However, it is not clear whether supplementary gene transfer can rescue significant morphological changes, caused by genetic deficits. In addition, with the transuterine gene transfer technique utilized in our previous report, the survival rate of embryos and their mothers after treatment was low, which became a serious obstacle for effective in vivo experiments. Here, we set out to elucidate the feasibility of supplementation therapy in Slc26a4 deficient mice, utilizing biphasic pulses, optimized by modifying pulse conditions. Modification of the biphasic pulse conditions during electroporation increased the survival rate. In addition, supplementation of the target gene cDNA into the otocysts of homozygous Slc24a4 knockout mice significantly prevented enlargement of the endolymphatic space in the inner ear areas; moreover, it rescued hearing and vestibular function of mice in vivo.

scholarly journals Adenovirus Vectors Target Several Cell Subtypes of Mammalian Inner Ear In Vivo

2016 ◽  
Vol 2016 ◽  
pp. 1-8 ◽  
Author(s):  
Yilai Shu ◽  
Yong Tao ◽  
Wenyan Li ◽  
Jun Shen ◽  
Zhengmin Wang ◽  
...  
Keyword(s):  
Inner Ear ◽  
Fluorescent Protein ◽  
Cell Types ◽  
Sensory Epithelium ◽  
Specific Cell ◽  
Supporting Cells ◽  
Auditory Hair Cells ◽  
A Genome ◽  
Adenovirus Vectors

Mammalian inner ear harbors diverse cell types that are essential for hearing and balance. Adenovirus is one of the major vectors to deliver genes into the inner ear for functional studies and hair cell regeneration. To identify adenovirus vectors that target specific cell subtypes in the inner ear, we studied three adenovirus vectors, carrying a reporter gene encoding green fluorescent protein (GFP) from two vendors or with a genome editing gene Cre recombinase (Cre), by injection into postnatal days 0 (P0) and 4 (P4) mouse cochlea through scala media by cochleostomy in vivo. We found three adenovirus vectors transduced mouse inner ear cells with different specificities and expression levels, depending on the type of adenoviral vectors and the age of mice. The most frequently targeted region was the cochlear sensory epithelium, including auditory hair cells and supporting cells. Adenovirus with GFP transduced utricular supporting cells as well. This study shows that adenovirus vectors are capable of efficiently and specifically transducing different cell types in the mammalian inner ear and provides useful tools to study inner ear gene function and to evaluate gene therapy to treat hearing loss and vestibular dysfunction.

Implications of Ewald's Second Law for the Evaluation of Vestibular Function

1979 ◽  
Vol 87 (4) ◽  
pp. 453-458 ◽  
Author(s):  
Young S. Kim ◽  
Clifford G. Y. Lau ◽  
Herman A. Jenkins ◽  
Vicente Honrubia
Keyword(s):  
Vestibular System ◽  
Semicircular Canal ◽  
Piecewise Linear ◽  
Vestibular Function ◽  
Second Law ◽  
Horizontal Semicircular Canal ◽  
Transfer Characteristics ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex ◽  
Ewald’S Second Law

The significance of Ewald's second law in the evaluation of the vestibulo-ocular reflex (VOR) was Investigated using the transfer characteristics of the vestibular and VOR systems in normal rabbits and rabbits in which one horizontal semicircular canal had been blocked. The transfer characteristics of the vestibular system were derived from the experimental results reported by Goldberg and Fernandez in 1971. A comparison was made of the properties of the bilateral and monolateral VOR systems with the predictions of a piecewise linear model of the vestibular system. The data received quantitatively collaborate the prediction of Ewald's second law as ft applies to the VOR responses.

scholarly journals Vestibular Perception and Navigation in the Congenitally Blind

2007 ◽  
Vol 97 (6) ◽  
pp. 4341-4356 ◽  
Author(s):  
Barry M. Seemungal ◽  
Stefan Glasauer ◽  
Michael A. Gresty ◽  
Adolfo M. Bronstein
Keyword(s):  
Time Constant ◽  
Vestibular Function ◽  
Velocity Storage ◽  
Ocular Reflex ◽  
Nerve Signal ◽  
Vestibular Ocular Reflex ◽  
Congenitally Blind ◽  
Vestibular Perception ◽  
Regression Slopes ◽  
Angular Displacements

Vestibular input is required for accurate locomotion in the dark, yet blind subjects’ vestibular function is unexplored. Such investigation may also identify visually dependent aspects of vestibular function. We assessed vestibular function perceptually in six congenitally blind (and 12 sighted) subjects. Cupula deflection by a transient angular, horizontal acceleration generates a related vestibular nerve signal that declines exponentially with time constant ≈4–7 s, which is prolonged to 15 s in the evoked vestibular-ocular reflex by the brain stem “velocity storage.” We measured perceptual velocity storage in blind subjects following velocity steps (overall perceptual vestibular time constant, experiment 1) and found it to be significantly shorter (5.34 s; range: 2.39–8.58 s) than in control, sighted subjects (15.8 s; P < 0.001). Vestibular navigation was assessed by subjects steering a motorized Bárány-chair in response to imposed angular displacements in a path-reversal task, “go-back-to-start” (GBS: experiment 2); and a path-completion task, “complete-the-circle” (CTC: experiment 3). GBS performances (comparing response vs. stimulus displacement regression slopes and r2) were equal between groups ( P > 0.05), but the blind showed worse CTC performance ( P < 0.05). Two blind individuals showed ultrashort perceptual time constants, high lifetime physical activity scores and superior CTC performances; we speculate that these factors may be inter-related. In summary, the vestibular velocity storage as measured perceptually is visually dependent. Early blindness does not affect path reversal performance but is associated with worse path completion, a task requiring an absolute spatial strategy. Although congenitally blind subjects are overall less able to utilize spatial mechanisms during vestibular navigation, prior extensive physical spatial activity may enhance vestibular navigation.

scholarly journals How do red-eyed treefrog embryos sense motion in predator attacks? Assessing the role of vestibular mechanoreception

2019 ◽  
Author(s):  
Julie Jung ◽  
Su J. Kim ◽  
Sonia M. Pérez Arias ◽  
James G. McDaniel ◽  
Karen M. Warkentin
Keyword(s):  
Vestibular System ◽  
Vestibular Function ◽  
Developmental Period ◽  
Limiting Factor ◽  
Environmental Cues ◽  
Physical Disturbance ◽  
Agalychnis Callidryas ◽  
Ocular Reflex ◽  
Vestibulo Ocular Reflex

ABSTRACTThe widespread ability to alter hatching timing in response to environmental cues can serve as a defense against threats to eggs. Arboreal embryos of red-eyed treefrogs, Agalychnis callidryas, hatch up to 30% prematurely to escape predation. This escape-hatching response is cued by physical disturbance of eggs during attacks, including vibrations or motion, and thus depends critically on mechanosensory ability. Predator-induced hatching appears later in development than flooding-induced, hypoxia-cued hatching; thus, its onset is not constrained by the development of hatching ability. It may, instead, reflect the development of mechanosensor function. We hypothesize that vestibular mechanoreception mediates escape-hatching in snake attacks, and that the developmental period when hatching-competent embryos fail to flee from snakes reflects a sensory constraint. We assessed the ontogenetic congruence of escape-hatching responses and an indicator of vestibular function, the vestibulo-ocular reflex (VOR), in three ways. First, we measured VOR in two developmental series of embryos 3–7 days old to compare with the published ontogeny of escape success in attacks. Second, during the period of greatest variation in VOR and escape success, we compared hatching responses and VOR across sibships. Finally, in developmental series, we compared the response of individual embryos to a simulated attack cue with their VOR. The onset of VOR and hatching responses were largely concurrent at all three scales. Moreover, latency to hatch in simulated attacks decreased with increasing VOR. These results are consistent with a key role of the vestibular system in the escape-hatching response of A. callidryas embryos to attacks.Red-eyed treefrogs’ hatching responses to predator attacks, vibration playbacks, and egg-jiggling appear when vestibular function develops. Ear development may be a key limiting factor in the onset of mechanosensory-cued hatching.

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