Search

The three-dimensional stria vascularis (SV) and cochlear blood vessel structure is essential for inner ear function. Here, modified Sca/eS, a sorbitol-based optical-clearing method, was reported to visualize SV and vascular structure in the intact mouse cochlea. Cochlear macrophages as well as perivascular-resident macrophage-like melanocytes were detected as GFP-positive cells of the CX3CR1+/GFP mice. This study’s method was effective in elucidating inner ear function under both physiological and pathological conditions.

Microglia, the only immune cells resident in the brain, actively participate in neural circuit maintenance by modifying synapses and neuronal excitability. Recent studies have revealed the differential gene expression and functional heterogeneity of microglia in different brain regions. The unique functions of the hippocampal neural network in learning and memory may be associated with the active roles of microglia in synapse remodeling. However, inflammatory responses induced by surgical procedures have been problematic in the two-photon microscopic analysis of hippocampal microglia. Here, a method is presented that enables the chronic observation of microglia in all layers of the hippocampal CA1 through an imaging window. This method allows the analysis of morphological changes in microglial processes for more than 1 month. Long-term and high-resolution imaging of the resting microglia requires minimally invasive surgical procedures, appropriate objective lens selection, and optimized imaging techniques. The transient inflammatory response of hippocampal microglia may prevent imaging immediately after surgery, but the microglia restore their quiescent morphology within a few weeks. Furthermore, imaging neurons simultaneously with microglia allows us to analyze the interactions of multiple cell types in the hippocampus. This technique may provide essential information about microglial function in the hippocampus.

Severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) is responsible for a pandemic affecting millions of people worldwide. Apart from the extreme global economic impact, the pandemic will likely have a lasting impact through long-term sequelae not yet fully understood. Fully understanding the mechanisms driving the various symptoms and sequelae of SARS-CoV-2 infection will allow for the eventual development of therapeutics to prevent or treat such life-altering symptoms. In this study, we developed a behavioral test of anosmia in SARS-CoV-2-infected hamsters. We find a moderately strong correlation between the level of anosmia and the score of histological damage within the olfactory epithelium. We also find a moderately strong correlation between the level of anosmia and the thickness of the olfactory epithelium, previously demonstrated to be severely damaged upon infection. Thus, this food-searching behavioral test can act as a simple and effective screening method in a hamster model for various therapeutics for SARS-CoV-2-related anosmia.

The impact of SARS-CoV-2 on the olfactory pathway was studied over several time points using Syrian golden hamsters. We found an incomplete recovery of the olfactory sensory neurons, prolonged activation of glial cells in the olfactory bulb, and a decrease in the density of dendritic spines within the hippocampus. These data may be useful for elucidating the mechanism underlying long-lasting olfactory dysfunction and cognitive impairment as a post-acute COVID-19 syndrome.

Lysosome-associated membrane protein 5 (LAMP5) is a mammalian ortholog of the Caenorhabditis elegans protein, UNC-46, which functions as a sorting factor to localize the vesicular GABA transporter UNC-47 to synaptic vesicles. In the mouse forebrain, LAMP5 is expressed in a subpopulation of GABAergic neurons in the olfactory bulb and the striato-nigral system, where it is required for fine-tuning of GABAergic synaptic transmission. Here we focus on the prominent expression of LAMP5 in the brainstem and spinal cord and suggest a role for LAMP5 in these brain regions. LAMP5 was highly expressed in several brainstem nuclei involved with auditory processing including the cochlear nuclei, the superior olivary complex, nuclei of the lateral lemniscus and grey matter in the spinal cord. It was localized exclusively in inhibitory synaptic terminals, as has been reported in the forebrain. In the absence of LAMP5, localization of the vesicular inhibitory amino acid transporter (VIAAT) was unaltered in the lateral superior olive and the ventral cochlear nuclei, arguing against a conserved role for LAMP5 in trafficking VIAAT. Lamp5 knockout mice showed no overt behavioral abnormality but an increased startle response to auditory and tactile stimuli. In addition, LAMP5 deficiency led to a larger intensity-dependent increase of wave I, II and V peak amplitude of auditory brainstem response. Our results indicate that LAMP5 plays a pivotal role in sensorimotor processing in the brainstem and spinal cord. Electronic supplementary material The online version of this article (10.1186/s13041-019-0437-4) contains supplementary material, which is available to authorized users.

Background In humans, it is well known that females have better hearing than males. The mechanism of this influence of sex on auditory function in humans is not well understood. Testing the hypothesis of underlying mechanisms often relies on preclinical research, a field in which sex bias still exists unconsciously. Rodents are popular research models in hearing, thus it is crucial to understand the sex differences in these rodent models when studying health and disease in humans. Objectives This review aims to summarize the existing sex differences in the auditory functions of rodent species including mouse, rat, Guinea pig, Mongolian gerbil, and chinchilla. In addition, a concise summary of the hearing characteristics and the advantages and the drawbacks of conducting auditory experiments in each rodent species is provided. Designs Manuscripts were identified in PubMed and Ovid Medline for the queries “Rodent”, “Sex Characteristics”, and “Hearing or Auditory Function”. Manuscripts were included if they were original research, written in English, and use rodents. The content of each manuscript was screened for the sex of the rodents and the discussion of sex-based results. Conclusions The sex differences in auditory function of rodents are prevalent and influenced by multiple factors including physiological mechanisms, sex-based anatomical variations, and stimuli from the external environment. Such differences may play a role in understanding and explaining sex differences in hearing of humans and need to be taken into consideration for developing clinical therapies aim to improve auditory performances.

Olfactory dysfunction is one of the most frequent and specific symptoms of coronavirus disease 2019 (COVID-19). Information on the damage and repair of the neuroepithelium and its impact on olfactory function after COVID-19 is still incomplete. While severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) causes the ongoing worldwide outbreak of COVID-19, little is known about the changes triggered by SARS-CoV-2 in the olfactory epithelium (OE) at the cellular level. Here, we report profiles of the OE after SARS-CoV-2 infection in golden Syrian hamsters, which is a reliable animal model of COVID-19. We observed severe damage in the OE as early as 3 days postinoculation and regionally specific damage and regeneration of the OE within the nasal cavity; the nasal septal region demonstrated the fastest recovery compared to other regions in the nasal turbinates. These findings suggest that anosmia related to SARS-CoV-2 infection may be fully reversible.

The STAT1 knock-out (KO) mouse is a frequently used transgenic immunodeficient strain to model human viral and bacterial diseases. The Lassa fever model was established in the STAT1 KO mice mimicking phenotypes seen in human patients including deafness in survivors. This model develops hearing loss at high prevalence and is a valuable tool to investigate viral infection-induced hearing loss. However, Lassa virus is a highly contagious and regulated agent requiring the unique logistics of the biosafety level 4 posing limitations for experimental work. Therefore, we did a detailed auditory analysis of the STAT1 KO mice to assess baseline auditory function in preparation for further auditory behavioral studies. Auditory brainstem response and distortion product otoacoustic emission tests were performed on males and females of the STAT1 KO mice and was compared to 129S6/SvEv wild type (WT) mice. The male WT mice had the best auditory performance and the female WT mice had the worst hearing performance. The male and female STAT1 KO mice had similar auditory performance to each other, which was intermediate between WT males and females. We conclude that both male and female STAT1 KO mice are suitable for studying viral infection-induced hearing loss.

The highly organized spatial arrangement of sensory hair cells in the organ of Corti is essential for inner ear function. Here, we report a new analytical pipeline, based on optical clearing of tissue, for the construction of a single-cell resolution map of the organ of Corti. A sorbitol-based optical clearing method enabled imaging of the entire cochlea at subcellular resolution. High-fidelity detection and analysis of all hair cell positions along the entire longitudinal axis of the organ of Corti were performed automatically by machine learning–based pattern recognition. Application of this method to samples from young, adult, and noise-exposed mice extracted essential information regarding cellular pathology, including longitudinal and radial spatial characteristics of cell loss, implying that multiple mechanisms underlie clustered cell loss. Our method of cellular mapping is effective for system-level phenotyping of the organ of Corti under both physiological and pathological conditions.

Here, we describe a sorbitol-based optical clearing method, called modified Sca/eS that can be used to image all hair cells (HCs) in the mouse cochlea. This modification of Sca/eS is defined by three steps: decalcification, de-lipidation, and refractive index matching, which can all be completed within 72 h. Furthermore, we established automated analysis programs that perform machine learning-based pattern recognition. These programs generate 1) a linearized image of HCs, 2) the coordinates of HCs, 3) a holocochleogram, and 4) clusters of HC loss. In summary, a novel approach that integrates modified Sca/eS and programs based on machine learning facilitates quantitative and comprehensive analysis of the physiological and pathological properties of all HCs.

Visual Abstract, Catecholaminergic (dopamine and norepinephrine) projections to the cortex play an important role in cognitive functions and dysfunctions including learning, addiction, and mental disorders. While dynamics of glutamatergic synapses have been well studied in such contexts, little is known regarding catecholaminergic projections, owing to lack of robust methods. Here we report a system to monitor catecholaminergic projections in vivo over the timeframes that such events occur. Green fluorescent protein (GFP) expression driven by tyrosine hydroxylase promoter in a transgenic mouse line enabled us to perform two-photon imaging of cortical catecholaminergic projections through a cranial window. Repetitive imaging of the same axons over 24 h revealed the highly dynamic nature of catecholaminergic boutons. Surprisingly, administration of single high dose methamphetamine (MAP) induced a transient increase in bouton volumes. This new method opens avenues for longitudinal in vivo evaluation of structural changes at single release sites of catecholamines in association with physiology and pathology of cortical functions.

Acoustic reflex is a sensitive indicator of middle ear lesions when the tympanic membrane is in-tact and tympanometry is normal. Acoustic reflex is not usually observed in conductive hearing loss caused by disruption of the ossicular chain including ossicular discontinuity and fixation. Ossicular disruption can show at least partially intact acoustic reflex under a certain condition. Moreover, ossicular discontinuity with a nearly intact acoustic reflex is quite rare and there have been few reports published to date. We here present a rare case of conductive hearing loss with a nearly intact acoustic reflex, and the patient was surgically confirmed to have ossicular discontinuity.

An 18-year-old patient presented with a major complaint of a mass in the right side of the neck. At the previous clinic, the patient underwent an open biopsy because the mass could not be diagnosed by fine needle aspiration. The patient was introduced to our institution after mass was diagnosed as ganglioneuroma by open biopsy. In our outpatient clinic, magnetic resonance imaging (MRI) and computed tomography (CT) were performed. Gradual growth of the mass was accompanied by sleep apnea syndrome. Ultimately, the patient was only able to sleep with nasal continuous positive airway pressure. Pathological examination confirmed the ganglioneuroma. MRI revealed expansion of the ganglioneuroma from the nasopharynx to the right upper mediastinum, occupying the surroundings of the contralateral carotid artery via the retropharyngeal space. CT revealed a tumor mass of 160 mm × 60 mm × 190 mm in size. The mass was surgically resected without any postoperative neurological disorder including Horner syndrome. The clinical course was successful without recurrence. This is the first report of a successful treatment of a large ganglineuroma that had continuously expanded to the contralateral neck via the retropharyngeal space.

Background and objectives:Organised haematomas of the maxillary sinus are rare, non-neoplastic, haemorrhagic lesions which can extend into the nasal cavity and/or the other paranasal sinuses. This study aimed to investigate the pathology of maxillary sinus organised haematoma, and also proposes a new aetiological hypothesis based on the observed pathology.Methods:Biopsies, computed tomography, magnetic resonance imaging and post-surgical histopathological examination of resected specimens were carried out.Conclusion:Distinct pathological differences were observed between the basal and peripheral portions of organised haematomas. We propose that an organised haematoma originates from the exudation of blood components between vascular endothelial cells. As a result, the basal portion consists of aggregated, dilated vessels around the natural ostium of the maxillary sinus. In addition, pseudovessels, without endothelial cells, arise from endocapillary vessels within the haematoma. Exudation of additional blood components from the pseudovessels advances the growth of the organised haematoma.

In this article we describe 5 rare cases of mumps-associated pharyngolaryngeal edema. To the best of our knowledge, this report includes the first case of mumps-associated pharyngolaryngeal edema in a patient who had previously received mumps vaccination, and these cases represent the sixth report of mumps-associated pharyngolaryngeal edema in the English literature. All 5 of our patients with mumps infection were adults and manifested airway stenosis due to pharyngolaryngeal edema. This edema responded favorably to steroid treatment without tracheotomy. We conclude that a pharyngolaryngeal examination is recommended for patients with mumps infection. Steroid treatment is usually effective against pharyngolaryngeal edema; however, in certain cases tracheotomy may be inevitable.

Hearing loss is the most frequent sensory disorder in humans. Auditory hair cells (HCs) are postmitotic at late-embryonic differentiation and postnatal stages, and their damage is the major cause of hearing loss. There is no measurable HC regeneration in the mammalian cochlea, and the maintenance of cell function is crucial for preservation of hearing. Here we generated mice deficient in autophagy-related 5 (Atg5), a gene essential for autophagy, in the HCs to investigate the effect of basal autophagy on hearing acuity. Deletion of Atg5 resulted in HC degeneration and profound congenital hearing loss. In autophagy-deficient HCs, polyubiquitinated proteins and p62/SQSTM1, an autophagy substrate, accumulated as inclusion bodies during the first postnatal week, and these aggregates increased in number. These findings revealed that basal autophagy has an important role in maintenance of HC morphology and hearing acuity.

Recurrent meningitis resulting from a partial defect of the stapedial footplate is most frequently treated by complete obliteration of the inner ear. Herein, we report the use of a partial obliteration technique in which the fistula is plugged with a shaped incus.A 5-year-old girl and a 7-year-old boy who had congenital inner ear malformations both developed recurrent meningitis. High-resolution computed tomography (HRCT) revealed soft tissue opacities between the mastoid air cells and the mesotympanum. Exploratory tympanotomies were performed, revealing cerebrospinal fluid (CSF) leakages from fistulae at the stapes footplate in both patients.In each case, the vestibule was partially obliterated with temporalis fascia and modified incus remnant. Bone dust and fibrin were also applied.Recurrence of CSF leakage and patient symptoms.None of the patients exhibited vertigo or dizziness after surgery, and meningitis did not recur during the follow-up period.Compete obliteration of the inner ear space can be avoided by using this technique, thereby leaving room for future cochlear implantation in addition to reducing direct injury to the vestibular system.

Preliminary Study of the Safety of Seasonal Allergic Rhinitis Treatment in Railway Personnel Objectives: The aim of the present survey was to develop guidelines for appropriate seasonal allergic rhinitis (SAR) treatment for railway personnel. The East Japan Railway Company (JR-EAST) carries the most passengers (6 billion per year) of any company worldwide. This was the first trial designed to assess the efficacy and safety of intranasal corticosteroids (INS) in JR-EAST drivers and conductors. Methods: A prospective series of 55 JR-EAST employees diagnosed with SAR by otorhinolaryngologists was studied. INS alone were administered as soon as symptoms were noted, immediately after the start of cedar pollen dispersal. The treatment periods were 1 week and, 2, 3, 4 and 8 weeks. Efficacy as the primary endpoint was assessed using the Japanese Rhinoconjuctivitis Quality of life Questionnaire (JRQLQ). Safety as the second endpoint was assessed by monitoring adverse events. Results: All 25 items of the JRQLQ improved significantly (p

Interleukin (IL)-33 is a novel member of the IL-1 cytokine family and a ligand for the orphan IL-1 family receptor ST2. IL-33 induces T helper 2-type inflammatory responses and is considered to play a crucial role in allergic inflammatory reactions such as asthma and atopic dermatitis. However, the role of IL-33 and its receptor ST2 in chronic rhinosinusitis remains unclear.In vitro study.The expression patterns of IL-33 and ST2 at both mRNA and protein levels in nasal polyps from eosinophilic chronic rhinosinusitis (ECRS) patients (n = 10) and non-ECRS patients (n = 13), as well as in seemingly normal mucosa of the uncinate processes in patients without sinusitis (control; n = 5), were compared using immunohistochemical staining, enzyme-linked immunosorbent assay, and real-time polymerase chain reactions.ST2-positive cells in the inflammatory cells in the subepithelial layer were significantly higher in the ECRS group than other groups. The expression of ST2 mRNA in polyps of the ECRS group was significantly increased compared with controls. Many ST2-positive eosinophils were observed in the mucosa of ECRS but not in the mucosa of non-ECRS patients. The expression level of IL-33 mRNA was not significantly different among the three groups.The current study suggests that IL-33 and its receptor ST2 may play important roles in the pathogenesis of chronic rhinosinusitis, especially in ECRS, through the increased expression of ST2 in eosinophils.N/A.

OBJECTIVE To describe the clinical course and treatment of a patient presenting with thrombophlebitis of the head and the neck with eosinophilic otitis media (EOM). PATIENT The patient was a 32-year-old woman with bronchial asthma and chronic sinusitis. She was treated for EOM, which presented as intractable otitis media with viscous effusion. Subsequently, she experienced sudden onset of nausea and headache. No signs of improvement were observed after the intravenous administration of several antibiotics. Magnetic resonance imaging (MRI) revealed right thrombophlebitis extending from the sigmoid sinus to the jugular vein. INTERVENTIONS Systemic administration of adrenocortical steroid hormone after intravenous antibiotic therapy. MAIN OUTCOME MEASURES Radiologic features and patient symptoms. RESULTS Intravenous antibiotic therapy was ineffective, but the patient's symptoms were relieved less than 1 day after the initiation of prednisolone treatment (30 mg/d for 5 d). MRI performed 3 days after treatment revealed that thrombophlebitis of the head and neck had disappeared. CONCLUSION Adrenocortical steroid hormone therapy may be an effective treatment for thrombophlebitis with EOM. Chemoattractants activated by EOM might be associated with the pathogenesis of thrombophlebitis of the head and neck.

To obtain actinomycetes capable of producing new enzyme affectors such as enzyme inhibitors or activators, a screening test was carried out. Streptomyces sp. strain No. BR-1381 isolated in our laboratory produced a proteinous lipase activator abbreviated as LAV. LAV was purified from the culture filtrate by salting-out with ammonium sulfate, DEAE-cellulose column chromatography and gel filtration on Sephadex G-100. LAV was stable in the pH range from 3 to 7 at 37°c for 20 hr and in a wider range of pH at 4°C for 5 days. LAV itself was very stable against heat treatment, but LAV did not have any effect on the thermal stability of Phycomyces nitens lipase. LAV activated several microbial lipases, but did not activate pancreatic or rice bran lipases. LAV particularly showed strong activation for Phycomyces nitens lipase.