Jaro-Journal of the Association for Research in Otolaryngology最新文献

{"title":"The Origin Along the Cochlea of Otoacoustic Emissions Evoked by Mid-Frequency Tone Pips.","authors":"Shawn S Goodman, Shannon M Lefler, Choongheon Lee, John J Guinan, Jeffery T Lichtenhan","doi":"10.1007/s10162-024-00955-0","DOIUrl":"10.1007/s10162-024-00955-0","url":null,"abstract":"<p><strong>Purpose: </strong>Tone-pip-evoked otoacoustic emissions (PEOAEs) are transient-evoked otoacoustic emissions (OAEs) that are hypothesized to originate from reflection of energy near the best-frequency (BF) cochlear place of the stimulus frequency. However, individual PEOAEs have energy with a wide range of delays. We sought to determine whether some PEOAE energy is consistent with having been generated far from BF.</p><p><strong>Methods: </strong>PEOAEs from 35 and 47 dB SPL tone pips were obtained by removing pip-stimulus energy by subtracting the ear-canal sound pressure from scaled-down 59 dB SPL tone pips (which evoke relatively small OAEs). PEOAE delays were measured at each peak in the PEOAE absolute-value waveforms. While measuring PEOAEs and auditory-nerve compound action potentials (CAPs), amplification was blocked sequentially from apex to base by cochlear salicylate perfusion. The perfusion time when a CAP was reduced identified when the perfusion reached the tone-pip BF place. The perfusion times when each PEOAE peak was reduced identified where along the cochlea it received cochlear amplification. PEOAEs and CAPs were measured simultaneously using one pip frequency in each ear (1.4 to 4 kHz across 16 ears).</p><p><strong>Results: </strong>Most PEOAE peaks received amplification primarily between the BF place and 1-2 octaves basal of the BF place. PEOAE peaks with short delays received amplification basal of BF place. PEOAE peaks with longer delays sometimes received amplification apical of BF place, consistent with previous stimulus-frequency-OAE results.</p><p><strong>Conclusion: </strong>PEOAEs provide information about cochlear amplification primarily within ~ 1.5 octave of the tone-pip BF place, not about regions > 3 octaves basal of BF.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"363-376"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349973/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141473065","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The Rapid Decline in Interaural-Time-Difference Sensitivity for Pure Tones Can Be Explained by Peripheral Filtering.","authors":"Matthew J Goupell, G Christopher Stecker, Brittany T Williams, Anhelina Bilokon, Daniel J Tollin","doi":"10.1007/s10162-024-00949-y","DOIUrl":"10.1007/s10162-024-00949-y","url":null,"abstract":"<p><strong>Purpose: </strong>The interaural time difference (ITD) is a primary horizontal-plane sound localization cue computed in the auditory brainstem. ITDs are accessible in the temporal fine structure of pure tones with a frequency of no higher than about 1400 Hz. How listeners' ITD sensitivity transitions from very best sensitivity near 700 Hz to impossible to detect within 1 octave currently lacks a fully compelling physiological explanation. Here, it was hypothesized that the rapid decline in ITD sensitivity is dictated not by a central neural limitation but by initial peripheral sound encoding, specifically, the low-frequency (apical) portion of the cochlear excitation pattern produced by a pure tone.</p><p><strong>Methods: </strong>ITD sensitivity was measured in 16 normal-hearing listeners as a joint function of frequency (900-1500 Hz) and level (10-50 dB sensation level).</p><p><strong>Results: </strong>Performance decreased with increasing frequency and decreasing sound level. The slope of performance decline was 90 dB/octave, consistent with the low-frequency slope of the cochlear excitation pattern.</p><p><strong>Conclusion: </strong>Fine-structure ITD sensitivity near 1400 Hz may be conveyed primarily by \"off-frequency\" activation of neurons tuned to lower frequencies near 700 Hz. Physiologically, this could be realized by having neurons sensitive to fine-structure ITD up to only about 700 Hz. A more extreme model would have only a single narrow channel near 700 Hz that conveys fine-structure ITDs. Such a model is a major simplification and departure from the classic formulation of the binaural display, which consists of a matrix of neurons tuned to a wide range of relevant frequencies and ITDs.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"377-385"},"PeriodicalIF":2.4,"publicationDate":"2024-08-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11349958/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141072414","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tinnitus in Children.","authors":"Derek J Hoare, Harriet Smith, Veronica Kennedy, Kathryn Fackrell","doi":"10.1007/s10162-024-00944-3","DOIUrl":"10.1007/s10162-024-00944-3","url":null,"abstract":"<p><p>This perspective reviews the current state of the art and literature on tinnitus in children, prevalence and risk factors, clinical management, and future priorities for healthcare provision and research. Most research in the field to date appears to be prevalence studies, which have reached dramatically different estimates; this reflects the lack of a standard language when asking about the presence of tinnitus, or how bothersome, distressing, or negatively impacting it is for the child. Estimates are also likely affected by a lack of awareness of tinnitus amongst children and parents. Children are less likely to spontaneously report tinnitus than adults, and parents are often unaware their child could even develop tinnitus, considering it a disease of older age for example. It is critical that children are asked and learn about tinnitus. In hearing clinics, clinicians should routinely ask about all children about tinnitus and offer tinnitus care and settings that are child- and family-friendly. As well as asking directly, clinicians should be alert to soft signs of tinnitus such as unexplained listening, speech perception, concentration difficulties, worry or anxiety, or difficulties completing hearing tests or using hearing aids. The recently developed impact of Tinnitus in Children Questionnaire (iTICQ) can then be used to assess problems that are most commonly core to children's experience of tinnitus. Clinical guidelines for tinnitus in children are few but provide recommendations for additional paediatric questionnaires and alternative assessments and for a range of treatment options. Of note, however, is the lack of clinical trials and, therefore, evidence of the effectiveness of any treatment for tinnitus in children. Significant and concerted work is therefore needed to raise awareness of tinnitus in children, understand the scale of clinical need, and standardise and evaluate clinical management options.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"239-247"},"PeriodicalIF":2.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150219/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140856742","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tinnitus: Clinical Insights in Its Pathophysiology-A Perspective.","authors":"Berthold Langguth, Dirk de Ridder, Winfried Schlee, Tobias Kleinjung","doi":"10.1007/s10162-024-00939-0","DOIUrl":"10.1007/s10162-024-00939-0","url":null,"abstract":"<p><p>Tinnitus, the perception of sound without a corresponding external sound source, and tinnitus disorder, which is tinnitus with associated suffering, present a multifaceted clinical challenge due to its heterogeneity and its incompletely understood pathophysiology and especially due to the limited therapeutic options. In this narrative review, we give an overview on various clinical aspects of tinnitus including its heterogeneity, contributing factors, comorbidities and therapeutic pathways with a specific emphasis on the implications for its pathophysiology and future research directions. Tinnitus exhibits high perceptual variability between affected individuals (heterogeneity) and within affected individuals (temporal variability). Hearing loss emerges as predominant risk factor and the perceived pitch corresponds to areas of hearing loss, supporting the compensatory response theory. Whereas most people who have tinnitus can live a normal life, in 10-20% tinnitus interferes severely with quality of life. These patients suffer frequently from comorbidities such as anxiety, depression or insomnia, acting as both risk factors and consequences. Accordingly, neuroimaging studies demonstrate shared brain networks between tinnitus and stress-related disorders shedding light on the intricate interplay of mental health and tinnitus. The challenge lies in deciphering causative relationships and shared pathophysiological mechanisms. Stress, external sounds, time of day, head movements, distraction, and sleep quality can impact tinnitus perception. Understanding these factors provides insights into the interplay with autonomic, sensory, motor, and cognitive processes. Counselling and cognitive-behavioural therapy demonstrate efficacy in reducing suffering, supporting the involvement of stress and anxiety-related networks. Hearing improvement, especially through cochlear implants, reduces tinnitus and thus indirectly validates the compensatory nature of tinnitus. Brain stimulation techniques can modulate the suffering of tinnitus, presumably by alteration of stress-related brain networks. Continued research is crucial for unravelling the complexities of tinnitus. Progress in management hinges on decoding diverse manifestations, identifying treatment-responsive subtypes, and advancing targeted therapeutic approaches.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"249-258"},"PeriodicalIF":2.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150221/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140295391","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Mechanical Effects of Medical Device Attachment to Human Tympanic Membrane.","authors":"Arash Ebrahimian, Hossein Mohammadi, Nima Maftoon","doi":"10.1007/s10162-024-00942-5","DOIUrl":"10.1007/s10162-024-00942-5","url":null,"abstract":"<p><strong>Purpose: </strong>Several treatment methods for hearing disorders rely on attaching medical devices to the tympanic membrane. This study aims to systematically analyze the effects of the material and geometrical properties and location of the medical devices attached to the tympanic membrane on middle-ear vibrations.</p><p><strong>Methods: </strong>A finite-element model of the human middle ear was employed to simulate the effects of attachment of medical devices. Various types of material and geometrical properties, locations, and modeling scenarios were investigated for the medical device.</p><p><strong>Results: </strong>The attachment of the device magnifies the effects of anti-resonances of the middle ear. Additionally, the variations of the material properties of the device significantly alter the middle-ear resonance frequency while changes in the umbo and stapes footplate motions are negligible at frequencies above 5 kHz. Furthermore, modeling the device as a point mass cannot accurately represent the implanted middle-ear behavior. The variations of the diameter and height of the medical device have negligible effects on the middle-ear vibrations at frequencies below 200 Hz but can have considerable impacts at higher frequencies. The effects of changing the device height were negligible at frequencies above 2 kHz. We also discuss the effects of medical device attachment on the vibration patterns of the tympanic membrane as well as the impacts of the variations of the location of the device on the stapes footplate responses.</p><p><strong>Conclusion: </strong>The findings of our study aid the development and optimization of new therapeutic devices, attached to the tympanic membrane, to have the least adverse effects on middle-ear vibrations.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"285-302"},"PeriodicalIF":2.4,"publicationDate":"2024-06-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11150348/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140337844","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tinnitus: A Dimensionally Segregated, yet Perceptually Integrated Heterogeneous Disorder.","authors":"Anusha Yasoda-Mohan, Katherine Adcock, Sook Ling Leong, Emma Meade, Berthold Langguth, Martin Schecklmann, Hubert Lim, Sven Vanneste","doi":"10.1007/s10162-023-00923-0","DOIUrl":"10.1007/s10162-023-00923-0","url":null,"abstract":"<p><strong>Objectives: </strong>Tinnitus subtypes are proposed to lie on a continuum of different symptom dimensions rather than be categorical. However, there is no comprehensive empirical data showing this complex relationship between different tinnitus symptoms. The objective of this study is to provide empirical evidence for the dimensional nature of tinnitus and how different auditory and non-auditory symptoms interact with each other through complex interactions. We do this using graph theory, a mathematical tool that empirically maps this complex interaction. This way, graph theory can be utilised to highlight a new and possibly important outlook on how we can understand the heterogeneous nature of tinnitus.</p><p><strong>Design: </strong>In the current study, we use the screening databases of the Treatment Evaluation of Neuromodulation for Tinnitus-Stage A1 (TENT-A1) and A2 (TENT-A2) randomised trials to delineate the dimensional relationship between different clinical measures of tinnitus as a secondary data analysis. We first calculate the empirical relationship by computing the partial correlation. Following this, we use different measures of centrality to describe the contribution of different clinical measures to the overall network. We also calculate the stability of the network and compare the similarity and differences between TENT-A1 and TENT-A2.</p><p><strong>Results: </strong>Components of the auditory subnetwork (loudness discomfort level, sound sensitivity, average hearing loss and high frequency hearing loss) are highly inter-connected in both networks with sound sensitivity and loudness discomfort level being highly influential with high measures of centrality. Furthermore, the relationship between the densely connected auditory subnetwork with tinnitus-related distress seems to vary at different levels of distress, hearing loss, duration and age of the participants.</p><p><strong>Conclusion: </strong>Our findings provide first-time evidence for tinnitus varying in a dimensional fashion illustrating the heterogeneity of this phantom percept and its ability to be perceptually integrated, yet behaviourally segregated on different symptomatic dimensions.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"215-227"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139492816","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Measuring Optokinetic Reflex and Vestibulo-Ocular Reflex in Unilateral Vestibular Organ Damage Model of Zebrafish.","authors":"Kang Hyeon Lim, Hong Ki Kim, Saemi Park, Eunjung Han, Insik Song, Hee Soo Yoon, Jaeyoung Kim, Yunkyoung Lee, Yong Hun Jang, Yoon Chan Rah, Sang Hyun Lee, June Choi","doi":"10.1007/s10162-024-00936-3","DOIUrl":"10.1007/s10162-024-00936-3","url":null,"abstract":"<p><p>One-sided vestibular disorders are common in clinical practice; however, their models have not been fully established. We investigated the effect of unilateral or bilateral deficits in the vestibular organs on the vestibulo-ocular reflex (VOR) and optokinetic reflex (OKR) of zebrafish using in-house equipment. For physical dislodgement of the otoliths in the utricles of zebrafish larvae, one or both utricles were separated from the surrounding tissue using glass capillaries. The video data from VOR and OKR tests with the larvae was collected and processed using digital signal processing techniques such as fast Fourier transform and low-pass filters. The results showed that unilateral and bilateral damage to the vestibular system significantly reduced VOR and OKR. In contrast, no significant difference was observed between unilateral and bilateral damage. This study confirmed that VOR and OKR were significantly reduced in zebrafish with unilateral and bilateral vestibular damage. Follow-up studies on unilateral vestibular disorders can be conducted using this tool.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"167-177"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018730/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139742827","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Frequency-Following Responses in Sensorineural Hearing Loss: A Systematic Review.","authors":"Laura Jacxsens, Lana Biot, Carles Escera, Annick Gilles, Emilie Cardon, Vincent Van Rompaey, Willem De Hertogh, Marc J W Lammers","doi":"10.1007/s10162-024-00932-7","DOIUrl":"10.1007/s10162-024-00932-7","url":null,"abstract":"<p><strong>Purpose: </strong>This systematic review aims to assess the impact of sensorineural hearing loss (SNHL) on various frequency-following response (FFR) parameters.</p><p><strong>Methods: </strong>Following PRISMA guidelines, a systematic review was conducted using PubMed, Web of Science, and Scopus databases up to January 2023. Studies evaluating FFRs in patients with SNHL and normal hearing controls were included.</p><p><strong>Results: </strong>Sixteen case-control studies were included, revealing variability in acquisition parameters. In the time domain, patients with SNHL exhibited prolonged latencies. The specific waves that were prolonged differed across studies. There was no consensus regarding wave amplitude in the time domain. In the frequency domain, focusing on studies that elicited FFRs with stimuli of 170 ms or longer, participants with SNHL displayed a significantly smaller fundamental frequency (F₀). Results regarding changes in the temporal fine structure (TFS) were inconsistent.</p><p><strong>Conclusion: </strong>Patients with SNHL may require more time for processing (speech) stimuli, reflected in prolonged latencies. However, the exact timing of this delay remains unclear. Additionally, when presenting longer stimuli (≥ 170 ms), patients with SNHL show difficulties tracking the F₀ of (speech) stimuli. No definite conclusions could be drawn on changes in wave amplitude in the time domain and the TFS in the frequency domain. Patient characteristics, acquisition parameters, and FFR outcome parameters differed greatly across studies. Future studies should be performed in larger and carefully matched subject groups, using longer stimuli presented at the same intensity in dB HL for both groups, or at a carefully determined maximum comfortable loudness level.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"131-147"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018579/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139708693","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Exploring the Use of Interleaved Stimuli to Measure Cochlear-Implant Excitation Patterns.","authors":"François Guérit, John C Middlebrooks, Robin Gransier, Matthew L Richardson, Jan Wouters, Robert P Carlyon","doi":"10.1007/s10162-024-00937-2","DOIUrl":"10.1007/s10162-024-00937-2","url":null,"abstract":"<p><strong>Purpose: </strong>Attempts to use current-focussing strategies with cochlear implants (CI) to reduce neural spread-of-excitation have met with only mixed success in human studies, in contrast to promising results in animal studies. Although this discrepancy could stem from between-species anatomical and aetiological differences, the masking experiments used in human studies may be insufficiently sensitive to differences in excitation-pattern width.</p><p><strong>Methods: </strong>We used an interleaved-masking method to measure psychophysical excitation patterns in seven participants with four masker stimulation configurations: monopolar (MP), partial tripolar (pTP), a wider partial tripolar (pTP + 2), and, importantly, a condition (RP + 2) designed to produce a broader excitation pattern than MP. The probe was always in partial-tripolar configuration.</p><p><strong>Results: </strong>We found a significant effect of stimulation configuration on both the amount of on-site masking (mask and probe on same electrode; an indirect indicator of sharpness) and the difference between off-site and on-site masking. Differences were driven solely by RP + 2 producing a broader excitation pattern than the other configurations, whereas monopolar and the two current-focussing configurations did not statistically differ from each other.</p><p><strong>Conclusion: </strong>A method that is sensitive enough to reveal a modest broadening in RP + 2 showed no evidence for sharpening with focussed stimulation. We also showed that although voltage recordings from the implant accurately predicted a broadening of the psychophysical excitation patterns with RP + 2, they wrongly predicted a strong sharpening with pTP + 2. We additionally argue, based on our recent research, that the interleaved-masking method can usefully be applied to non-human species and objective measures of CI excitation patterns.</p>","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"201-213"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018570/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140066342","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Pneumococcal Meningitis Induces Hearing Loss and Cochlear Ossification Modulated by Chemokine Receptors CX3CR1 and CCR2.","authors":"Keiko Hirose, Song Zhe Li, Ruth Gill, Jared Hartsock","doi":"10.1007/s10162-024-00935-4","DOIUrl":"10.1007/s10162-024-00935-4","url":null,"abstract":"<p><strong>Purpose: </strong>Pneumococcal meningitis is a major cause of hearing loss and permanent neurological impairment despite widely available antimicrobial therapies to control infection. Methods to improve hearing outcomes for those who survive bacterial meningitis remains elusive. We used a mouse model of pneumococcal meningitis to evaluate the impact of mononuclear phagocytes on hearing outcomes and cochlear ossification by altering the expression of CX3CR1 and CCR2 in these infected mice.</p><p><strong>Methods: </strong>We induced pneumococcal meningitis in approximately 500 C57Bl6 adult mice using live Streptococcus pneumoniae (serotype 3, 1 × 10⁵ colony forming units (cfu) in 10 µl) injected directly into the cisterna magna of anesthetized mice and treated these mice with ceftriaxone daily until recovered. We evaluated hearing thresholds over time, characterized the cochlear inflammatory response, and quantified the amount of new bone formation during meningitis recovery. We used microcomputed tomography (microCT) scans to quantify cochlear volume loss caused by neo-ossification. We also performed perilymph sampling in live mice to assess the integrity of the blood-perilymph barrier during various time intervals after meningitis. We then evaluated the effect of CX3CR1 or CCR2 deletion in meningitis symptoms, hearing loss, macrophage/monocyte recruitment, neo-ossification, and blood labyrinth barrier function.</p><p><strong>Results: </strong>Sixty percent of mice with pneumococcal meningitis developed hearing loss. Cochlear fibrosis could be detected within 4 days of infection, and neo-ossification by 14 days. Loss of spiral ganglion neurons was common, and inner ear anatomy was distorted by scarring caused by new soft tissue and bone deposited within the scalae. The blood-perilymph barrier was disrupted at 3 days post infection (DPI) and was restored by seven DPI. Both CCR2 and CX3CR1 monocytes and macrophages were present in the cochlea in large numbers after infection. Neither chemokine receptor was necessary for the induction of hearing loss, cochlear fibrosis, ossification, or disruption of the blood-perilymph barrier. CCR2 knockout (KO) mice suffered the most severe hearing loss. CX3CR1 KO mice demonstrated an intermediate phenotype with greater susceptibility to hearing loss compared to control mice. Elimination of CX3CR1 mononuclear phagocytes during the first 2 weeks after meningitis in CX3CR1-DTR transgenic mice did not protect mice from any of the systemic or hearing sequelae of pneumococcal meningitis.</p><p><strong>Conclusions: </strong>Pneumococcal meningitis can have devastating effects on cochlear structure and function, although not all mice experienced hearing loss or cochlear damage. Meningitis can result in rapid progression of hearing loss with fibrosis starting at four DPI and ossification within 2 weeks of infection detectable by light microscopy. The inflammatory response to bacterial meningitis is r","PeriodicalId":56283,"journal":{"name":"Jaro-Journal of the Association for Research in Otolaryngology","volume":" ","pages":"179-199"},"PeriodicalIF":2.4,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11018586/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140112330","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}