Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

Li, Liling; Chen, Dan; Lin, Xuexin; Luo, Jia; Tan, Jingqian; Li, Peng

doi:10.1002/brx2.34

Cited by 5 publications

(3 citation statements)

References 141 publications

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“…SNHL is also associated with inflammation factors [ 41 ]. We selected classic inflammatory factors interleukin (IL)-6, tumor necrosis factor-alpha (TNF-α), and nuclear factor kappa B (NF-κB) related to SNHL.…”

Section: Discussionmentioning

confidence: 99%

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Gu,

Jiang,

Chen

et al. 2024

BMC Genomics

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Background The stria vascularis (SV), located in the lateral wall of the cochlea, maintains cochlear fluid homeostasis and mechanoelectrical transduction (MET) activity required for sound wave conduction. The pathogenesis of a number of human inheritable deafness syndromes, age related hearing loss, drug-induced ototoxicity and noise-induced hearing loss results from the morphological changes and functional impairments in the development of the SV. In this study, we investigate the implications of intercellular communication within the SV in the pathogenesis of sensorineural hearing loss (SNHL). We aim to identify commonly regulated signaling pathways using publicly available single-cell transcriptomic sequencing (scRNA-seq) datasets. Methods We analyzed scRNA-seq data, which was derived from studying the cochlear SV in mice with SNHL compared to normal adult mice. After quality control and filtering, we obtained the major cellular components of the mouse cochlear SV and integrated the data. Using Seurat's FindAllMarkers and FindMarkers packages, we searched for novel conservative genes and differential genes. We employed KEGG and GSEA to identify molecular pathways that are commonly altered among different types of SNHL. We utilized pySCENIC to discover new specific regulatory factors in SV subpopulation cells. With the help of CellChat, we identified changes in subpopulation cells showing similar trends across different SNHL types and their alterations in intercellular communication pathways. Results Through the analysis of the integrated data, we discovered new conserved genes to SV specific cells and identified common downregulated pathways in three types of SNHL. The enriched genes for these pathways showing similar trends are primarily associated with the Electron Transport Chain, related to mitochondrial energy metabolism. Using the CellChat package, we further found that there are shared pathways in the incoming signaling of specific intermediate cells in SNHL, and these pathways have common upstream regulatory transcription factor of Nfe2l2. Combining the results from pySCENIC and CellChat, we predicted the transcription factor Nfe2l2 as an upstream regulatory factor for multiple shared cellular pathways in IC. Additionally, it serves as an upstream factor for several genes within the Electron Transport Chain. Conclusion Our bioinformatics analysis has revealed that downregulation of the mitochondrial electron transport chain have been observed in various conditions of SNHL. E2f1, Esrrb, Runx1, Yy1, and Gata2 could serve as novel important common TFs regulating the electron transport chain. Adm has emerged as a potential new marker gene for intermediate cells, while Itgb5 and Tesc show promise as potential new marker genes for marginal cells in the SV. These findings offer a new perspective on SV lesions in SNHL and provide additional theoretical evidence for the same drug treatment and prevention of different pathologies of SNHL.

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Section: Discussionmentioning

confidence: 99%

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Gu,

Jiang,

Chen

et al. 2024

BMC Genomics

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“…Inflammation is a critical component in the pathogenesis of SSNHL ( 54 , 55 ). Understanding this process at local and systemic levels is fundamental to a better understanding of symptoms, prognosis and hearing recovery.…”

Section: Discussionmentioning

confidence: 99%

The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss

do Amaral,

Peron,

Soeiro

et al. 2024

Front. Neurol.

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IntroductionSudden sensorineural hearing loss (SSNHL) is a common emergency symptom in otolaryngology that requires immediate diagnosis and treatment. SSNHL has a multifactorial etiology, and its pathophysiologic mechanisms may be associated with inflammatory and metabolic changes that may affect the cochlear microenvironment or its nervous component, thus triggering the process or hindering hearing recovery. Therefore, the aim of this study was to assess metabolic and inflammatory changes to identify systemic parameters that could serve as prognostic factors for hearing recovery in patients with SSNHL.Materials and methodsThirty patients with a sudden hearing loss of at least 30 dB in three contiguous frequencies were enrolled in this study. Patients were followed up for 4 months and peripheral blood samples were collected at 7 days (V1), 30 days (V2) and 120 days (V3). Interleukins (IL)-1F7, IL-2, IL-4, IL-5, IL-6, IL-10, interferon γ (IFN-γ), tumor necrosis factor α (TNF-α) and adiponectin were quantified in serum. In addition, lipid and glycemic profiles as well as concentration of creatinine, uric acid, fructosamine, peroxide, total proteins and albumin were analyzed. Patients underwent weekly ear-specific hearing tests with standard pure tone thresholds for frequencies of 250–8,000 Hz, speech recognition threshold and word recognition score.ResultsPatients with SSNHL were divided into a group of patients who did not achieve hearing recovery (n = 14) and another group who achieved complete and significant recovery (n = 16). Most serologic parameters showed no significant changes or values indicating clinical changes. However, IFN-γ levels decreased by 36.3% between V1 and V2. The cytokine TNF-α showed a statistically significant decrease from V1 to V3 (from 22.91 to 10.34 pg./mL). Adiponectin showed a decrease from 553.7 ng/mL in V1 to 454.4 ng/mL in V3.DiscussionOur results show that serologic cytokine levels change in the acute phase of manifestation of SSNHL and establish a parallel between systemic changes and improvements in hearing, especially TNF-α, which showed differences in hearing recovery. The use of IFN-γ, TNF-α and adiponectin may elucidate the clinical improvement in these patients.

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“…Cochlear damage from insults such as acoustic trauma, is a multifaceted degenerative phenomenon caused by a cascade of detrimental responses such as oxidative stress, inflammation, and excitotoxicity, which ultimately result in both necrotic and apoptotic cell death ( Bohne et al, 2007 ; Yang et al, 2016 ; Kalinec et al, 2017 ; Arrigali and Serban, 2022 ; Paik et al, 2022 ; Xu et al, 2023 ). Both reactive oxygen species and inflammation have been identified as major contributors to hearing loss ( Li et al, 2023 ). Several studies have shown that noise-induced inflammatory responses in the cochlea are triggered by the recruitment of inflammatory cells such as macrophages, and the upregulation of pro-inflammatory cytokines ( Frye et al, 2019 ; Weiwei et al, 2020 ; Hough et al, 2022 ).…”

Section: Introductionmentioning

confidence: 99%

Hyaluronic acid-ibuprofen conjugation: a novel ototherapeutic approach protecting inner ear cells from inflammation-mediated damage

Birru,

Veit,

Arrigali

et al. 2024

Front. Pharmacol.

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There is a substantial need of effective drugs for the treatment of hearing loss, which affects nearly 500 million individuals globally. Hearing loss can be the result of intense or prolonged noise exposure, ototoxic drugs, infections, and trauma, which trigger inflammatory signaling cascades that lead to irreversible damage to cochlear structures. To address this, we developed and characterized a series of covalent conjugates of anti-inflammatory drugs to hyaluronic acid (HA), for potential use as topical ototherapeutics. These conjugates were tested in in vitro assays designed to mirror physiological processes typically observed with acoustic trauma. Intense noise exposure leads to macrophage recruitment to the cochlea and subsequent inflammatory damage to sensory cells. We therefore first tested our conjugates’ ability to reduce the release of inflammatory cytokines in macrophages. This anti-inflammatory effect on macrophages also translated to increased cochlear cell viability. In our initial screening, one conjugate, ibuprofen-HA, demonstrated significantly higher anti-inflammatory potential than its counterparts. Subsequent cytokine release profiling of ibuprofen-HA further confirmed its ability to reduce a wider range of inflammatory markers, to a greater extent than its equivalent unconjugated drug. The conjugate’s potential as a topical therapeutic was then assessed in previously developed tympanic and round window membrane tissue permeation models. As expected, our data indicate that the conjugate has limited tympanic membrane model permeability; however, it readily permeated the round window membrane model and to a greater extent than the unconjugated drug. Interestingly, our data also revealed that ibuprofen-HA was well tolerated in cellular and tissue cytocompatibility assays, whereas the unconjugated drug displayed significant cytotoxicity at equivalent concentrations. Moreover, our data highlighted the importance of chemical conjugation of ibuprofen to HA; the conjugate had improved anti-inflammatory effects, significantly reduced cytotoxicity, and is more suitable for therapeutic formulation. Overall, this work suggests that ibuprofen-HA could be a promising safe and effective topical ototherapeutic for inflammation-mediated cochlear damage.

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Understanding the role of inflammation in sensorineural hearing loss: Current goals and future prospects

Cited by 5 publications

References 141 publications

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

Identification of common stria vascularis cellular alteration in sensorineural hearing loss based on ScRNA-seq

The inflammatory and metabolic status of patients with sudden-onset sensorineural hearing loss

Hyaluronic acid-ibuprofen conjugation: a novel ototherapeutic approach protecting inner ear cells from inflammation-mediated damage

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