Quantitative definition of neurobehavior, vision, hearing and brain volumes in macaques congenitally exposed to Zika virus.

Congenital Zika virus (ZIKV) exposure results in a spectrum of disease ranging from severe birth defects to delayed onset neurodevelopmental deficits. ZIKV-related neuropathogenesis, predictors of birth defects, and neurodevelopmental deficits are not well defined in people. Here we assess the methodological and statistical feasibility of a congenital ZIKV exposure macaque model for identifying infant neurobehavior and brain abnormalities that may underlie neurodevelopmental deficits. We inoculated five pregnant macaques with ZIKV and mock-inoculated one macaque in the first trimester. Following birth, growth, ocular structure/function, brain structure, hearing, histopathology, and neurobehavior were quantitatively assessed during the first week of life. We identified the typical pregnancy outcomes of congenital ZIKV infection, with fetal demise and placental abnormalities. We estimated sample sizes needed to define differences between groups and demonstrated that future studies quantifying brain region volumes, retinal structure, hearing, and visual pathway function require a sample size of 14 animals per group (14 ZIKV, 14 control) to detect statistically significant differences in at least half of the infant exam parameters. Establishing the parameters for future studies of neurodevelopmental outcomes following congenital ZIKV exposure in macaques is essential for robust and rigorous experimental design.

Gender differences in audio-vestibular disorders.

In the last years, the attention to the role of gender in physiopathology and pharmacology of diseases in several medical disciplines is rising; however, the data on the relationship between gender and audio-vestibular disorders are still inconclusive and sometimes confusing. With this letter to the editor, we would like to review the role of gender in audio-vestibular disorders. Literature data show that anatomic variances of the inner ear do exist in men and women and that the different physiology and/or hormonal influence between genders could produce different clinical outcome of routine audiological and vestibular tests. Beyond the epidemiological gender-related differences, the clinical data suggest that the gender has a potential role as an etiopathogenetic factor in audio-vestibular disorders and it is probably responsible for the different clinical features observed between male and female subjects.

The Influence of Occupational Noise Exposure on Cardiovascular and Hearing Conditions among Industrial Workers.

This study was conducted to estimate the current prevalence of hypertension, cardiovascular condition and hearing difficulty of workers exposure to occupational noise, and to analyze any associations between these abnormal signs and occupational noise exposure. The subjects included 5205 noise-exposed workers. Workers with high noise exposure were more likely to have a higher threshold value than low exposure ones (P < 0.05). Subjects in the high exposure group had a significantly higher risk of hypertension and hearing loss than the ones in low exposure group. Between the ages of 30 and 45, high-level occupational noise exposure led to a significantly raising risk of both hypertension (Adjusted OR = 1.59, 95% CI, 1.19-2.11) and hearing loss (Adjusted OR = 1.28, 95% CI, 1.03-1.60) when comparing to low-level noise exposure. In male workers, the prevalence of hearing difficulty in high exposure group was approximately 1.2 times worse than in low group (P = 0.006). In addition, exposure to high noise level demonstrated a significant association with hypertension and hearing loss when the duration time to occupational noise was longer than 10 years. Hypertension and hearing difficulty is more prevalent in the noise-exposed group (higher than 85 dB[A]). Steps to reduce workplace noise levels and to improve workplace-based health are thus urgently needed.

Prevalence of permanent childhood hearing loss detected at the universal newborn hearing screen: Systematic review and meta-analysis.

CONTEXT: Permanent childhood hearing loss (PCHL) can affect speech, language, and wider outcomes. Adverse effects are mitigated through universal newborn hearing screening (UNHS) and early intervention. OBJECTIVE: We undertook a systematic review and meta-analysis to estimate prevalence of UNHS-detected PCHL (bilateral loss ≥26 dB HL) and its variation by admission to neonatal intensive care unit (NICU). A secondary objective was to report UNHS programme performance (PROSPERO: CRD42016051267). DATA SOURCES: Multiple electronic databases were interrogated in January 2017, with further reports identified from article citations and unpublished literature (November 2017). STUDY SELECTION: UNHS reports from very highly-developed (VHD) countries with relevant prevalence and performance data; no language or date restrictions. DATA EXTRACTION: Three reviewers independently extracted data and assessed quality. RESULTS: We identified 41 eligible reports from 32 study populations (1799863 screened infants) in 6195 non-duplicate references. Pooled UNHS-detected PCHL prevalence was 1.1 per 1000 screened children (95% confidence interval [CI]: 0.9, 1.3; I2 = 89.2%). This was 6.9 times (95% CI: 3.8, 12.5) higher among those admitted to NICU. Smaller studies were significantly associated with higher prevalences (Egger's test: p = 0.02). Sensitivity and specificity ranged from 89-100% and 92-100% respectively, positive predictive values from 2-84%, with all negative predictive values 100%. LIMITATIONS: Results are generalisable to VHD countries only. Estimates and inferences were limited by available data. CONCLUSIONS: In VHD countries, 1 per 1000 screened newborns require referral to clinical services for PCHL. Prevalence is higher in those admitted to NICU. Improved reporting would support further examination of screen performance and child demographics.

Epidermoid Cyst of the Cerebellopontine Angle Presenting with Contralateral Trigeminal Neuralgia: Extremely Rare Case and Review of Literature.

BACKGROUND: An epidermoid cyst is a rare tumor of the cerebellopontine angle region. It usually presents with ipsilateral compressive symptoms. The contralateral trigeminal neuralgia is an unusual presentation in such cases. We did not find such case reports in the literature. CASE DESCRIPTION: Here, we report a case of a 62-year-old female with a right cerebellopontine angle epidermoid cyst presenting with right hearing impairment and the contralateral trigeminal neuralgia. CONCLUSION: The possible mechanism leading to the contralateral trigeminal neuralgia is discussed here along with the diagnosis and management of the case.

Transcriptomic analysis of chicken cochleae after gentamicin damage and the involvement of four signaling pathways (Notch, FGF, Wnt and BMP) in hair cell regeneration.

Unlike mammalian hair cells, which are essentially unable to regenerate after damage, avian hair cells have a robust capacity for regeneration. The prerequisite for understanding the above difference is knowing the genetic programming of avian hair cell regeneration. Although the major processes have been known, the precise molecular signaling that induces regeneration remains unclear. To address this issue, we performed a high-throughput transcriptomic analysis of gene expression during hair cell regeneration in the chick cochlea after antibiotic injury in vivo. A total of 16,588 genes were found to be expressed in the cochlea, of which about 1000 genes were differentially expressed among the four groups studied, i.e., 2 days (d) or 3 d post-treatment with gentamicin or physiological saline. The differentially expressed genes were distributed across approximately one hundred signaling pathways, including the Notch, MAPK (FGF), Wnt and TGF-ß (BMP) pathways that have been shown to play important roles in embryonic development. Some differentially expressed genes (2-3 in each pathway) were further verified by qRT-PCR. After blocking Notch, FGF or BMP signaling, the number of regenerating hair cells and mitotic supporting cells increased. However, the opposite effect was observed after suppressing the Wnt pathway or enhancing BMP signaling. To our knowledge, the present study provided a relatively complete dataset of candidate genes and signaling pathways most likely involved in hair cell regeneration and should be a useful start in deciphering the genetic circuitry for inducing hair cell regeneration in the chick cochlea.

Advances in translational inner ear stem cell research.

Stem cell research is expanding our understanding of developmental biology as well as promising the development of new therapies for a range of different diseases. Within hearing research, the use of stem cells has focused mainly on cell replacement. Stem cells however have a broad range of other potential applications that are just beginning to be explored in the ear. Mesenchymal stem cells are an adult derived stem cell population that have been shown to produce growth factors, modulate the immune system and can differentiate into a wide variety of tissue types. Potential advantages of mesenchymal/adult stem cells are that they have no ethical constraints on their use. However, appropriate regulatory oversight seems necessary in order to protect patients from side effects. Disadvantages may be the lack of efficacy in many preclinical studies. But if proven safe and efficacious, they are easily translatable to clinical trials. The current review will focus on the potential application on mesenchymal stem cells for the treatment of inner ear disorders.

Global Analysis of Protein Expression of Inner Ear Hair Cells.

The mammalian inner ear (IE) subserves auditory and vestibular sensations via highly specialized cells and proteins. Sensory receptor hair cells (HCs) are necessary for transducing mechanical inputs and stimulating sensory neurons by using a host of known and as yet unknown protein machinery. To understand the protein composition of these unique postmitotic cells, in which irreversible protein degradation or damage can lead to impaired hearing and balance, we analyzed IE samples by tandem mass spectrometry to generate an unbiased, shotgun-proteomics view of protein identities and abundances. By using Pou4f3/eGFP-transgenic mice in which HCs express GFP driven by Pou4f3, we FACS purified a population of HCs to analyze and compare the HC proteome with other IE subproteomes from sensory epithelia and whole IE. We show that the mammalian HC proteome comprises hundreds of uniquely or highly expressed proteins. Our global proteomic analysis of purified HCs extends the existing HC transcriptome, revealing previously undetected gene products and isoform-specific protein expression. Comparison of our proteomic data with mouse and human databases of genetic auditory/vestibular impairments confirms the critical role of the HC proteome for normal IE function, providing a cell-specific pool of candidates for novel, important HC genes. Several proteins identified exclusively in HCs by proteomics and verified by immunohistochemistry map to human genetic deafness loci, potentially representing new deafness genes. SIGNIFICANCE STATEMENT: Hearing and balance rely on specialized sensory hair cells (HCs) in the inner ear (IE) to convey information about sound, acceleration, and orientation to the brain. Genetically and environmentally induced perturbations to HC proteins can result in deafness and severe imbalance. We used transgenic mice with GFP-expressing HCs, coupled with FACS sorting and tandem mass spectrometry, to define the most complete HC and IE proteome to date. We show that hundreds of proteins are uniquely identified or enriched in HCs, extending previous gene expression analyses to reveal novel HC proteins and isoforms. Importantly, deafness-linked proteins were significantly enriched in HCs, suggesting that this in-depth proteomic analysis of IE sensory cells may hold potential for deafness gene discovery.

Neurociencia y Educación: ¿podemos ir de la investigación básica a su aplicación? Un posible marco de referencia desde la investigación en dislexia1 / Neurociencia y Educación: ¿podemos ir de la investigación básica a su aplicación? Un posible marco de referencia desde la investigación en dislexia

La neurociencia podría transformar la educación, pues proporciona nuevos métodos para comprender el aprendizaje y el desarrollo cognitivo, sus mecanismos causales y una forma empírica de evaluar la eficacia de diferentes pedagogías. No obstante, éste sería un objetivo a largo plazo. Desde la neurociencia educativa se debería empezar estudiando cómo los sistemas cognitivos se construyen sobre los sensoriales a lo largo del desarrollo. Aquí me centraré en el lenguaje. Pequeñas diferencias individuales iniciales en una función sensorial, por ejemplo la auditiva, podrían ser el origen de notables diferencias individuales en el desarrollo lingüístico. La neurociencia podría proporcionar una comprensión detallada de los mecanismos causales del desarrollo que vinculan la audición, el desarrollo fonológico y el desarrollo de la alfabetización. Este tipo de investigación neurocientífica básica podría orientar al campo de la educación y la pedagogía explorando los efectos que sobre estos mecanismos ejercen diferentes contextos pedagógicos y de aprendizaje

Neuroscience has the potential to transform education because it provides novel methods for understanding human learning and cognitive development. It therefore offers deeper understanding of causal mechanisms in learning and an empirical approach to evaluating the efficacy of different pedagogies. However, this will be a long-term enterprise and there will be few immediate pay-offs. Here I set out one possible framework for linking basic research in neuroscience to pedagogical questions in education. I suggest that the developing field of educational neuroscience must first study how sensory systems build cognitive systems over developmental time. I focus on one cognitive system, language, the efficient functioning of which is critical for reading acquisition. Small initial differences in sensory function, for example auditory function, have the potential to cause large differences in linguistic performance over the learning trajectory. The tools offered by neuroscience can enable better understanding of the causal developmental mechanisms linking audition, phonological development and literacy development, in fine-grained detail. Following this basic research, neuroscience can then inform education and pedagogy by exploring the effects on these neural mechanisms of different learning contexts and pedagogies

Valoración del dolor en el anciano / Assessment of pain in the elderly

Un porcentaje variable entre el 50 al 80% de los mayores de 65 años sufren dolor. Según los datos epidemiológicos el dolor aumenta en pacientes ancianos y frágiles. La prevalencia de pluripatología, deterioro funcional y fragilidad aumenta con la edad. Las barreras que existen por parte de pacientes, sanitarios y administraciones en cuanto a los tratamientos farmacológicos dificultan el adecuado control del dolor. La evaluación y determinación de la causa del dolor es la clave para conseguir su control. Su evaluación debe incluir historia clínica, exploración, test diagnósticos y algunas escalas. La elección del instrumento depende del nivel cognitivo, visual, auditivo y capacidad comunicativa de cada paciente (AU)

Pain is suffered by 50-80% of the population older than 65. Epidemiological data suggests increasing prevalence of chronic pain and frailty with advancing age. Elderly patients are more likely to have multiple chronic health pathologies, declining function and frailty. The barriers present for patients, providers and health systems also negatively impact effective pain control. Pain assessment and determination of its mechanism is the key to optimal pain control. Pain can be rated using a medical history, physical examination, diagnostic test and some scales. Choices of pain measurement tools are dependent upon the patient´s cognitive, visual, auditory and communicative status (AU)

Intracochlear Bleeding Enhances Cochlear Fibrosis and Ossification: An Animal Study.

The aim of this study was to investigate the effects of intracochlear bleeding during cochleostomy on cochlear inflammatory response and residual hearing in a guinea pig animal model. Auditory brainstem response threshold shifts were greater in blood injected ears (p<0.05). Interleukin-1ß, interleukin-10, tumor necrosis factor-α and nitric oxide synthase 2, cytokines that are related to early stage inflammation, were significantly increased in blood injected ears compared to normal and cochleostomy only ears at 1 day after surgery; with the increased IL-1ß being sustained until 3 days after the surgery (p<0.05). Hair cells were more severely damaged in blood injected ears than in cochleostomy only ears. Histopathologic examination revealed more extensive fibrosis and ossification in blood injected ears than cochleostomy only ears. These results show that intracochlear bleeding enhanced cochlear inflammation resulting in increased fibrosis and ossification in an experimental animal model.

Central plasticity and dysfunction elicited by aural deprivation in the critical period.

The acoustic signal is crucial for animals to obtain information from the surrounding environment. Like other sensory modalities, the central auditory system undergoes adaptive changes (i.e., plasticity) during the developmental stage as well as other stages of life. Owing to its plasticity, auditory centers may be susceptible to various factors, such as medical intervention, variation in ambient acoustic signals and lesion of the peripheral hearing organ. There are critical periods during which auditory centers are vulnerable to abnormal experiences. Particularly in the early postnatal development period, aural inputs are essential for functional maturity of auditory centers. An aural deprivation model, which can be achieved by attenuating or blocking the peripheral acoustic afferent input to the auditory center, is ideal for investigating plastic changes of auditory centers. Generally, auditory plasticity includes structural and functional changes, some of which can be irreversible. Aural deprivation can distort tonotopic maps, disrupt the binaural integration, reorganize the neural network and change the synaptic transmission in the primary auditory cortex or at lower levels of the auditory system. The regulation of specific gene expression and the modified signal pathway may be the deep molecular mechanism of these plastic changes. By studying this model, researchers may explore the pathogenesis of hearing loss and reveal plastic changes of the auditory cortex, facilitating the therapeutic advancement in patients with severe hearing loss. After summarizing developmental features of auditory centers in auditory deprived animals and discussing changes of central auditory remodeling in hearing loss patients, we aim at stressing the significant of an early and well-designed auditory training program for the hearing rehabilitation.

Homozygosity for frameshift mutations in XYLT2 result in a spondylo-ocular syndrome with bone fragility, cataracts, and hearing defects.

Heparan and chondroitin/dermatan sulfated proteoglycans have a wide range of roles in cellular and tissue homeostasis including growth factor function, morphogen gradient formation, and co-receptor activity. Proteoglycan assembly initiates with a xylose monosaccharide covalently attached by either xylosyltransferase I or II. Three individuals from two families were found that exhibited similar phenotypes. The index case subjects were two brothers, individuals 1 and 2, who presented with osteoporosis, cataracts, sensorineural hearing loss, and mild learning defects. Whole exome sequence analyses showed that both individuals had a homozygous c.692dup mutation (GenBank: NM_022167.3) in the xylosyltransferase II locus (XYLT2) (MIM: 608125), causing reduced XYLT2 mRNA and low circulating xylosyltransferase (XylT) activity. In an unrelated boy (individual 3) from the second family, we noted low serum XylT activity. Sanger sequencing of XYLT2 in this individual revealed a c.520del mutation in exon 2 that resulted in a frameshift and premature stop codon (p.Ala174Profs(∗)35). Fibroblasts from individuals 1 and 2 showed a range of defects including reduced XylT activity, GAG incorporation of (35)SO4, and heparan sulfate proteoglycan assembly. These studies demonstrate that human XylT2 deficiency results in vertebral compression fractures, sensorineural hearing loss, eye defects, and heart defects, a phenotype that is similar to the autosomal-recessive disorder spondylo-ocular syndrome of unknown cause. This phenotype is different from what has been reported in individuals with other linker enzyme deficiencies. These studies illustrate that the cells of the lens, retina, heart muscle, inner ear, and bone are dependent on XylT2 for proteoglycan assembly in humans.

Aging of the auditory system.

Presbycusis or age-related hearing loss (ARHL) affects most elderly people. It is characterized by reduced hearing thresholds and speech understanding with the well-known negative consequences for communication and quality of social life. The hearing loss is connected to age-related histologic changes, as described and classified by Schuknecht. Aging itself is a multifactorial, genetically driven process that is influenced by oxidative stress that gradually leads to reduced endocochlear potential and cell loss of key players in sound transmission and supporting structures. Oxidative stress is caused by damaging factors like noise, infection, and other systemic factors. All reparative mechanisms in acute and chronic cochlear damage attempt to reduce oxidative stress and to balance inner-ear homeostasis. Accurate clinical assessment of ARHL starts with the differentiation between peripheral and central components. Treatment of the peripheral hearing loss often involves hearing aids, whereas auditory and psychologic training seems to be important in central auditory disturbance.

The relationship between jugular bulb position and jugular bulb related inner ear dehiscence: a retrospective analysis.

OBJECTIVE: High jugular bulb (HJB) can erode inner ear structures creating a jugular bulb related inner ear dehiscence (JBID). The aim of this study was to analyze the relationship between the position of jugular bulb (JB) and JBID using high-resolution computed tomography (HRCT). MATERIAL AND METHODS: In this retrospective study HRCT images of 552 ears of 276 patients with hearing loss, otogenic vertigo, tinnitus or idiopathic peripheral facial nerve paralysis were analyzed. HJB type-1 was defined when JB dome reached above the inferior part of the round window, but was below the inferior edge of the internal acoustic meatus (IAM). HJB type-2 was defined when the dome of JB was higher than the inferior edge of IAM. The frequencies and types of HJB were evaluated. JBID for each HJB type was determined. Frequencies of JBID eroding the vestibular aqueduct (VA), the cochlear aqueduct and the posterior semicircular canal were examined. RESULTS: HJB type-1 and HJB type-2 were found in 19% (105/552) and in 15.8% (87/552) of studied ears. JBID showed to be in 3.8% (21/552) of all ears. 90.5% (19/21) of JBID revealed eroding of VA. Jugular bulb related cochlear aqueduct dehiscence and jugular bulb related posterior semicircular canal dehiscence were found in one ear each. The frequency of jugular bulb related vestibular aqueduct dehiscence (JBVAD) in patients with HJB reaching above IAM was higher than in patients with HJB lower than IAM. CONCLUSIONS: HJB is common, but JBID is rare. JBID prevalently erodes VA. HJB rising above IAM is most at risk to show JBVAD.

Molecular profile of cochlear immunity in the resident cells of the organ of Corti.

BACKGROUND: The cochlea is the sensory organ of hearing. In the cochlea, the organ of Corti houses sensory cells that are susceptible to pathological insults. While the organ of Corti lacks immune cells, it does have the capacity for immune activity. We hypothesized that resident cells in the organ of Corti were responsible for the stress-induced immune response of the organ of Corti. This study profiled the molecular composition of the immune system in the organ of Corti and examined the immune response of non-immune epithelial cells to acoustic overstimulation. METHODS: Using high-throughput RNA-sequencing and qRT-PCR arrays, we identified immune- and inflammation-related genes in both the cochlear sensory epithelium and the organ of Corti. Using bioinformatics analyses, we cataloged the immune genes expressed. We then examined the response of these genes to acoustic overstimulation and determined how changes in immune gene expression were related to sensory cell damage. RESULTS: The RNA-sequencing analysis reveals robust expression of immune-related genes in the cochlear sensory epithelium. The qRT-PCR array analysis confirms that many of these genes are constitutively expressed in the resident cells of the organ of Corti. Bioinformatics analyses reveal that the genes expressed are linked to the Toll-like receptor signaling pathway. We demonstrate that expression of Toll-like receptor signaling genes is predominantly from the supporting cells in the organ of Corti cells. Importantly, our data demonstrate that these Toll-like receptor pathway genes are able to respond to acoustic trauma and that their expression changes are associated with sensory cell damage. CONCLUSION: The cochlear resident cells in the organ of Corti have immune capacity and participate in the cochlear immune response to acoustic overstimulation.

Newborn hearing screening and early diagnostic in the NICU.

The aim was to describe the outcome of neonatal hearing screening (NHS) and audiological diagnosis in neonates in the NICU. The sample was divided into Group I: neonates who underwent NHS in one step and Group II: neonates who underwent a test and retest NHS. NHS procedure was automated auditory brainstem response. NHS was performed in 82.1% of surviving neonates. For GI, referral rate was 18.6% and false-positive was 62.2% (normal hearing in the diagnostic stage). In GII, with retest, referral rate dropped to 4.1% and false-positive to 12.5%. Sensorineural hearing loss was found in 13.2% of infants and conductive in 26.4% of cases. There was one case of auditory neuropathy spectrum (1.9%). Dropout rate in whole process was 21.7% for GI and 24.03% for GII. We concluded that it was not possible to perform universal NHS in the studied sample or, in many cases, to apply it within the first month of life. Retest reduced failure and false-positive rate and did not increase evasion, indicating that it is a recommendable step in NHS programs in the NICU. The incidence of hearing loss was 2.9%, considering sensorineural hearing loss (0.91%), conductive (1.83%) and auditory neuropathy spectrum (0.19%).

A partial hearing animal model for chronic electro-acoustic stimulation.

OBJECTIVE: Cochlear implants (CIs) have provided some auditory function to hundreds of thousands of people around the world. Although traditionally carried out only in profoundly deaf patients, the eligibility criteria for implantation have recently been relaxed to include many partially-deaf patients with useful levels of hearing. These patients receive both electrical stimulation from their implant and acoustic stimulation via their residual hearing (electro-acoustic stimulation; EAS) and perform very well. It is unclear how EAS improves speech perception over electrical stimulation alone, and little evidence exists about the nature of the interactions between electric and acoustic stimuli. Furthermore, clinical results suggest that some patients that undergo cochlear implantation lose some, if not all, of their residual hearing, reducing the advantages of EAS over electrical stimulation alone. A reliable animal model with clinically-relevant partial deafness combined with clinical CIs is important to enable these issues to be studied. This paper outlines such a model that has been successfully used in our laboratory. APPROACH: This paper outlines a battery of techniques used in our laboratory to generate, validate and examine an animal model of partial deafness and chronic CI use. MAIN RESULTS: Ototoxic deafening produced bilaterally symmetrical hearing thresholds in neonatal and adult animals. Electrical activation of the auditory system was confirmed, and all animals were chronically stimulated via adapted clinical CIs. Acoustic compound action potentials (CAPs) were obtained from partially-hearing cochleae, using the CI amplifier. Immunohistochemical analysis allows the effects of deafness and electrical stimulation on cell survival to be studied. SIGNIFICANCE: This animal model has applications in EAS research, including investigating the functional interactions between electric and acoustic stimulation, and the development of techniques to maintain residual hearing following cochlear implantation. The ability to record CAPs via the CI has clinical direct relevance for obtaining objective measures of residual hearing.

Autologous meatal skin graft implantation and intratympanic injection of Pseudomonas aeruginosa: a new experimental mouse model of acquired middle ear cholesteatoma.

AIM: To create an experimental model for the biomedical research of middle ear cholesteatoma. METHODS: Cholesteatoma was induced in the right ears of mice. An autologous meatal skin graft was implanted into the middle ear via the tympanic membrane followed by an intratympanic injection of Pseudomonas aeruginosa. Six weeks after surgery, the formation of acquired cholesteatoma was evaluated by macroscopic examination, CT scan, and histological analysis. The expressions of TNF-α, IL-1ß, and IL-6 were measured with real-time PCR. Auditory-evoked brain stem response was used for assessing the changes in hearing levels. RESULTS: None of the mice died during the modeling time. By the sixth postoperative week, cholesteatoma had successfully formed in 23 out of 25 mice, which equals a success rate of 92%. A CT scan revealed that the cholesteatoma was eroding the cochlea. Furthermore, histological analysis demonstrated a cystic structure covered by stratified squamous epithelium and keratin desquamation in the lamellae inside the cystic cavity in the bullae. All mice with experimentally induced cholesteatoma showed hearing impairment and an upregulated expression of TNF-α, IL-1ß, and IL-6. CONCLUSION: The present study successfully developed a mouse model of acquired middle ear cholesteatoma, which provides an extremely valuable tool for auditory and biomedical research. The modeling approach is technically easy and has a high success rate.

Relationship between changes in the cochlear blood flow and disorder of hearing function induced by blast injury in guinea pigs.

The auditory system is the most susceptible to damages from blast waves. Blast injuries always lead to varying degrees of hearing impairment. Although a disorder of the cochlear blood flow (CoBF) has been considered to be related to many pathological processes of the auditory system and to contribute to various types of hearing loss, changes in the CoBF induced by blast waves and the relationship between such changes and hearing impairment are undefined. To observe the changes in the cochlear microcirculation after exposure to an explosion blast, investigate the relationship between changes in the CoBF and hearing impairment and subsequently explore the mechanism responsible for the changes in the CoBF, we detected the perfusion of the cochlear microcirculation and hearing threshold shift after exposure to an explosion blast. Then, an N-nitro-L-arginine-methyl ester (L-NAME, NO synthase inhibitor) solution and artificial perilymph were applied to the round window (RW) of the cochlea before the blast exposure, followed by an evaluation of the CoBF and hearing function. The results indicated that the changes in the CoBF were correlated to the strength of the blast wave. The cochlear blood flow significantly increased when the peak value of the blast overpressure was greater than approximately 45 kPa, and there was no significant change in the cochlear blood flow when the peak value of the blast overpressure was less than approximately 35 kPa. Following local administration of the NO synthase inhibitor L-NAME, the increase in the CoBF induced by the blast was inhibited, and this reduction was significantly associated with the hearing threshold.