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1.
J Immunol ; 208(4): 827-838, 2022 02 15.
Artigo em Inglês | MEDLINE | ID: mdl-35046106

RESUMO

Meniere's disease (MD) is a disorder of the inner ear characterized by episodes of spontaneous vertigo, fluctuating hearing loss, and tinnitus. Recent studies have demonstrated that IgE may play a role in the pathogenesis of MD. Patients with MD (n = 103), acoustic neuroma (n = 5), and healthy subjects (n = 72) were recruited into the study. Serum from the participants was analyzed for IgE and type 2-related cytokines. IgE and CD23 expression levels in vestibular end organs of patients, C57BL/6 mice, or mouse HEI-OC1 cells were analyzed. Finally, the role of CD23 in IgE transcytosis was assessed using HEI-OC1 cells. Serum IgE was elevated in patients with MD and positively correlated with clinical symptoms. IL-4, IL-5, IL-10, IL-13, and CD23 levels were increased in patients with MD compared with the control group. In the transcytosis assay, mouse IgE was found to be bidirectionally transported across the HEI-OC1 cell monolayer. Additionally, CD23 downregulation using a small interfering RNA approach significantly reduced the efficiency of IgE transcytosis, suggesting that IgE is transported by CD23. Furthermore, exposure to IL-4 increased CD23 expression and enhanced IgE transcytosis in the HEI-OC1 cells and primary vestibular end organs. Our study indicated that IgE may play a role in the pathophysiology of MD. In addition, CD23-mediated IgE transcytosis in the hair cells may play a critical role in initiating inflammation in the inner ear. Thus, reducing the level of IgE may be a potentially effective approach for MD treatment.


Assuntos
Orelha Interna/imunologia , Orelha Interna/metabolismo , Imunoglobulina E/imunologia , Lectinas Tipo C/metabolismo , Doença de Meniere/etiologia , Doença de Meniere/metabolismo , Receptores de IgE/metabolismo , Adulto , Idoso , Animais , Biomarcadores , Citocinas/metabolismo , Modelos Animais de Doenças , Suscetibilidade a Doenças , Feminino , Imunofluorescência , Humanos , Imunoglobulina E/metabolismo , Lectinas Tipo C/genética , Masculino , Doença de Meniere/diagnóstico , Camundongos , Pessoa de Meia-Idade , Imagem Molecular , Fenótipo , Ligação Proteica , Transporte Proteico , Receptores de IgE/genética , Transcitose/imunologia , Vestíbulo do Labirinto/imunologia , Vestíbulo do Labirinto/metabolismo , Vestíbulo do Labirinto/patologia
2.
Eur Arch Otorhinolaryngol ; 281(8): 4029-4038, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38341823

RESUMO

PURPOSE: This retrospective cohort study aimed to investigate the effect of minimally invasive cochlear implantation (CI) on the vestibular function (VF) and residual hearing (RH) as well as their relationship in pediatric recipients before and after surgery. METHODS: Twenty-four pediatric patients with preoperative low frequency residual hearing (LFRH) (250 or 500 Hz ≤ 80 dB HL) who underwent minimally invasive CI were enrolled. Pure-tone thresholds, the cervical/ocular vestibular-evoked myogenic potential (cVEMP/oVEMP), and video head impulse test (vHIT) were all evaluated in the 24 pediatric patients with preoperative normal VF before and at 1 and 12 months after surgery. The relationship between changes in hearing and VF was analyzed preoperatively and at 1 and 12 months postoperatively. RESULTS: There were no significant differences on VF preservation and hearing preservation (HP) at both 1 and 12 months post-CI (p > 0.05). At 1 month post-CI, the correlations of the variations in vestibulo-ocular reflex (VOR) gains of horizontal semicircular canal (HSC) and posterior semicircular canal (PSC) and the shift in 250 Hz threshold were negatively correlated (r = - 0.41, p = 0.04 and r = - 0.43, p = 0.04, respectively). At 12 months post-CI, the shift in 250 Hz threshold negatively correlated to the variations in VOR gain of superior semicircular canal (SSC) (r = - 0.43, p = 0.04); the HP positively correlated to the variation in oVEMP-amplitude ratio (AR) (r = 0.41, p = 0.04). CONCLUSION: Our study confirmed that there were partial correlations between VF preservation and HP both in the short- and long-terms after atraumatic CI surgery, especially with the 250 Hz threshold. Regarding the variation of PSC function, the correlation with hearing status was variable with time after atraumatic CI surgery. Minimally invasive techniques for HP are successful and effective for the preservation of VF in pediatric patients both in the short- and long-terms.


Assuntos
Implante Coclear , Procedimentos Cirúrgicos Minimamente Invasivos , Potenciais Evocados Miogênicos Vestibulares , Humanos , Implante Coclear/métodos , Feminino , Masculino , Estudos Retrospectivos , Procedimentos Cirúrgicos Minimamente Invasivos/métodos , Pré-Escolar , Criança , Potenciais Evocados Miogênicos Vestibulares/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Audiometria de Tons Puros , Resultado do Tratamento , Audição/fisiologia , Testes de Função Vestibular , Teste do Impulso da Cabeça/métodos , Vestíbulo do Labirinto/fisiopatologia , Vestíbulo do Labirinto/cirurgia , Lactente
3.
Am J Physiol Cell Physiol ; 320(1): C132-C141, 2021 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33175573

RESUMO

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 also plays a role in ciliogenesis, orientation of cilia basal feet, and planar polarity. Sensory cells of the inner ear display unique structural features that underlie their mechanosensitivity. They represent a distinctive form of cellular polarity, known as planar cell polarity (PCP). However, a role for Spag6 in the inner ear has not yet been explored. In the present study, the function of Spag6 in the inner ear was examined using Spag6-deficient mice. Our results demonstrate hearing loss in the Spag6 mutants, associated with abnormalities in cellular patterning, cell shape, stereocilia bundles, and basal bodies, as well as abnormally distributed Frizzled class receptor 6 (FZD6), suggesting that Spag6 participates in PCP regulation. Moreover, we found that the subapical microtubule meshwork was disrupted. Our observations suggest new functions for Spag6 in hearing and PCP in the inner ear.


Assuntos
Polaridade Celular , Células Ciliadas Auditivas Internas/metabolismo , Perda Auditiva/metabolismo , Audição , Proteínas dos Microtúbulos/deficiência , Microtúbulos/metabolismo , Animais , Feminino , Receptores Frizzled/metabolismo , Células Ciliadas Auditivas Internas/ultraestrutura , Perda Auditiva/genética , Perda Auditiva/patologia , Perda Auditiva/fisiopatologia , Masculino , Camundongos da Linhagem 129 , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteínas dos Microtúbulos/genética , Microtúbulos/ultraestrutura
4.
J Pharmacol Sci ; 147(4): 325-330, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34663514

RESUMO

Spag6 encodes an axoneme central apparatus protein that is required for normal flagellar and cilia motility. Recent findings suggest that Spag6 plays a role in hearing and planar cell polarity (PCP) in the cochlea of the inner ear. However, a role for Spag6 in the vestibule has not yet been explored. In the present study, the function of Spag6 in the vestibule of the inner ear was examined using Spag6-deficient mice. Our results demonstrate a vestibular disorder in the Spag6 mutants, associated with abnormal ultrastructures of vestibular hair cells and Scarpa's ganglion cells, including swollen stereocilia, decreased crista in mitochondria and swollen Scarpa's ganglion cells. Immunostaining data suggests existence of caspase-dependent apoptosis in vestibular sensory epithelium and Scarpa's ganglion cells. Our observations reveal new functions for Spag6 in vestibular function and apoptosis in the mouse vestibule.


Assuntos
Apoptose/genética , Proteínas dos Microtúbulos/genética , Mutação , Doenças Vestibulares/genética , Animais , Polaridade Celular/genética , Cóclea/citologia , Cóclea/fisiologia , Feminino , Células Ciliadas Vestibulares/patologia , Audição/genética , Masculino , Camundongos Transgênicos , Doenças Vestibulares/patologia , Nervo Vestibular/citologia , Nervo Vestibular/patologia
5.
Neural Plast ; 2016: 4280407, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27057364

RESUMO

Whole organ culture of the spiral ganglion region is a resourceful model system facilitating manipulation and analysis of live sprial ganglion neurons (SGNs). Three-dimensional (3D) cultures have been demonstrated to have many biomedical applications, but the effect of 3D culture in maintaining the SGNs structure and function in explant culture remains uninvestigated. In this study, we used the matrigel to encapsulate the spiral ganglion region isolated from neonatal mice. First, we optimized the matrigel concentration for the 3D culture system and found the 3D culture system protected the SGNs against apoptosis, preserved the structure of spiral ganglion region, and promoted the sprouting and outgrowth of SGNs neurites. Next, we found the 3D culture system promoted growth cone growth as evidenced by a higher average number and a longer average length of filopodia and a larger growth cone area. 3D culture system also significantly elevated the synapse density of SGNs. Last, we found that the 3D culture system combined with neurotrophic factors had accumulated effects in promoting the neurites outgrowth compared with 3D culture or NFs treatment only groups. Together, we conclude that the 3D culture system preserves the structure and function of SGN in explant culture.


Assuntos
Técnicas de Cultura de Células/métodos , Sobrevivência Celular/efeitos dos fármacos , Fatores de Crescimento Neural/farmacologia , Neurônios/citologia , Gânglio Espiral da Cóclea/citologia , Animais , Células Cultivadas , Colágeno , Combinação de Medicamentos , Laminina , Camundongos , Neuritos/efeitos dos fármacos , Neuritos/fisiologia , Neurônios/efeitos dos fármacos , Neurônios/fisiologia , Proteoglicanas , Gânglio Espiral da Cóclea/efeitos dos fármacos , Gânglio Espiral da Cóclea/fisiologia , Sinapses/efeitos dos fármacos , Sinapses/fisiologia
6.
J Headache Pain ; 17(1): 81, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27600145

RESUMO

BACKGROUND: Neurotrophic factors have been implicated in hyperalgesia and peripheral levels of these molecules are altered in migraine pathophysiology. Artemin, a vasculature-derived neurotrophic factor, contributes to pain modulation and trigeminal primary afferent sensitization through binding its selective receptor GFRα3. The distribution of artemin and GFRα3 in the dura mater raises an anatomy supports that they may be involved in migraine. In this study we evaluated the expression of artemin and GFRα3 in an animal migraine model that may be relevant for migraine. METHODS: In this study, using a rat migraine model by administration of nitroglycerin (NTG), we investigated the expression of artemin in the dura mater and GFRα3 in the trigeminal ganglia (TG) by means of quantitative reverse transcription-polymerase chain reaction, western blot and immunofluorescence labeling. RESULTS: Artemin immunoreactivity was found in the smooth muscle cells of dural vasculature and GFRα3 was present in cytoplasm of TG neurons. The mRNA levels of artemin and GFRα3 were significantly elevated after NTG treatment at 2 and 4 h respectively (P < 0.05). The expression of artemin protein was increased at 4 h and continually up to 8 h in the dura mater following NTG administration (P < 0.05). The expression of GFRα3 protein was elevated at 4 h and continually up to 10 h in the TG following NTG administration (P < 0.05). CONCLUSION: The findings suggest that artemin and GFRα3 play an important role in the pathogenesis of migraine and may represent potential therapeutic targets for the treatment of migraine.


Assuntos
Dura-Máter/metabolismo , Receptores de Fator Neurotrófico Derivado de Linhagem de Célula Glial/metabolismo , Transtornos de Enxaqueca/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Gânglio Trigeminal/metabolismo , Animais , Modelos Animais de Doenças , Masculino , Transtornos de Enxaqueca/induzido quimicamente , Ratos , Ratos Wistar
7.
Transl Pediatr ; 13(3): 492-498, 2024 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-38590371

RESUMO

Background: Typical Ménière's disease (MD) rarely occurs in childhood. Compared to adults, age-associated changes in vestibular function can occur during infancy and childhood. Previous case reports may have lacked some audiovestibular tests in children. It is worthwhile to follow a child with MD to observe how vertigo and hearing loss could progress under an insufficient vestibular system. Case Description: A 14-year-old pediatric patient with disassociated episodes between vertigo and hearing loss was finally diagnosed with MD. He was diagnosed with probable MD due to lack of objective evidence of hearing loss in his first two admissions. However, in his third admission, he had hearing loss even without attack of vertigo and was finally diagnosed. By listing the patient's audiovestibular auxiliary tests in a chronological order, we might follow the progress of pediatric MD. Gadolinium-enhanced magnetic resonance imaging (Gd-MRI) might be sensitive to reflect endolymphatic hydrops (EH). Medications including corticosteroids might be effective for both hearing loss and vertigo. Conclusions: In pediatric MD, vestibular and cochlear symptoms may occur and progress independently. Audiovestibular evaluation, especially caloric tests and cervical vestibular evoked myogenic potential (cVEMP), can be useful for pediatric MD. Gd-MRI can be sensitive for detecting EH. Both systemic and postauricular administration of corticosteroids might be effective in alleviating vertigo and improving hearing. Prolongation of the follow-up period of pediatric MD is warranted.

8.
Gland Surg ; 13(6): 999-1015, 2024 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-39015705

RESUMO

Background: There have been studies on the role of sperm-associated antigen 6 (SPAG6) in cytoskeleton formation and growth cone stability, but it is also unknown how spag6 affect tumor growth and development. The aim of this study was to clarify the role of SPAG6 in pan-cancer, with some findings about thyroid carcinoma (THCA) validated through experiments. Methods: We examined the role of SPAG6 in pan-cancer, with the data being collected from databases. Further analysis was conducted to assess its correlations with prognosis, gene heterogeneity, stemness, and tumor immunity. The interacting proteins of SPAG6 were also identified, and gene ontology enrichment analysis was performed to determine its biological function. We preliminarily confirmed the role of SPAG6 via in vitro experiments and immunofluorescence staining. Results: This study found that SPAG6 expression was differentially expressed in cancers and at various tumor stages and grades. In stomach and esophageal carcinoma (STES), stomach adenocarcinoma (STAD), kidney renal clear cell carcinoma (KIRC), lung squamous cell carcinoma (LUSC), and adrenocortical carcinoma (ACC), SPAG6 expression was correlated with gender. SPAG6 expression was also found to be correlated with prognostic value, with low expression being associated with poor prognosis. Furthermore, SPAG6 expression was positively linked with immune-related cells in HNSC, chemokine receptors in LUSC, and immune checkpoint genes in THCA. Furthermore, SPAG6 overexpression suppressed the malignant phenotypes of THCA cells, manifested by slower proliferation and decreased migration. The different SPAG6 expression in THCA led to different malignant phenotypes, which are involved in the upregulation of DNA repair, MYC targets, peroxisome, and G2M checkpoint. Conclusions: SPAG6 plays a significant role as an oncogene and can be used as a marker to predict the prognosis of cancer. SPAG6 influences both the tumor immune infiltration and microenvironment, making it a promising immunotherapeutic target for tumor therapy.

9.
Laryngoscope ; 134(1): 410-418, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37314111

RESUMO

OBJECTIVE: We investigated correlations among clinical features, degree of inner ear endolymphatic hydrops (EH), and hippocampal volume (HV) in different stages of Meniere's disease (MD). METHODS: From February 2021 to April 2022, clinical data were collected from 99 patients (39 males, 60 females, mean age: 50.4 ± 10.0 [range: 26-69] years) with unilateral MD admitted to the Department of Vertigo Disease of Shandong ENT Hospital. The left and right ears were affected in 64 and 35 patients, respectively. There were 50 and 49 cases in early (Stages 1, 2) and late stages (Stages 3, 4), respectively. Fifty healthy participants were included as controls. Audiovestibular function test results, EH grading using gadolinium-enhanced magnetic resonance imaging (MRI), and HV determined on MRI were analyzed for patients at different stages of MD. RESULTS: Between-group comparisons of early and late MD revealed significant differences in the disease course, vestibular function (VF), degree of EH, and HV. There were no significant between-group differences based on age, sex, affected side, subjective degree of dizziness, hospital anxiety, or depression. Mean HV in patients with early-stage MD was correlated with the canal paresis value of the caloric test and pure tone hearing threshold, HV in late-stage patients was correlated with vestibular EH. CONCLUSION: Patients with late-stage MD exhibited severe auditory and VF impairments, increased EH, and atrophy of the HV. More advanced disease was associated with greater vestibular damage and degree of EH. LEVEL OF EVIDENCE: 3 Laryngoscope, 134:410-418, 2024.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Vestíbulo do Labirinto , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Doença de Meniere/complicações , Doença de Meniere/diagnóstico por imagem , Hidropisia Endolinfática/diagnóstico por imagem , Hidropisia Endolinfática/complicações , Vestíbulo do Labirinto/diagnóstico por imagem , Vertigem/complicações , Atrofia/complicações , Hipocampo/diagnóstico por imagem , Hipocampo/patologia , Imageamento por Ressonância Magnética/métodos
10.
OTO Open ; 8(3): e171, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39050361

RESUMO

Background: Meniere disease, characterized by intermittent episodes of vertigo, fluctuating sensorineural hearing loss, tinnitus, and aural pressure, is a common cause of vertigo in humans. The pathogenesis of Meniere disease remains unknown. The current study aimed to describe a novel pathological change discovered in the inner ears of patients with Meniere disease who underwent labyrinthectomy. Methods: This retrospective case-control study was conducted with 21 patients with MD who underwent labyrinthectomy. A total of 15 patients diagnosed with acoustic neuroma or glomus jugular tumor were review over the same period of time as control. The clinical information of the patients and the pathological features of the membrane are described. Results: The new pathological tissue was a morbid membrane structure sealing the round window, characterized by the formation of lymphatic capillaries. Histochemical and immunofluorescent staining was positive for D2-40, LYVE-1, podoplanin, and PROX1, which are the classical markers of the lymphatic vessels. Transmission electron microscopy revealed that the lymph capillaries lacked a typical basement membrane and that their ends were blind, composed of a single layer of endothelial cells with valval connection structures between adjacent capillary epithelial cells. Conclusion: This is the first report of lymphatic vessels in the human inner ear, and this pathological structure is a completely new discovery. The lymphatic vessels may develop due to inflammation or decompensation of pressure in the inner ear, suggesting that the inner ear can reactively form lymphatic vessels in some inflammation and fluid flow-dependent pathological conditions. The current findings help in improving our understanding of the pathogenesis of Meniere disease.

11.
Laryngoscope Investig Otolaryngol ; 9(4): e1313, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-39171095

RESUMO

Objective: To retrospectively analyze clinical features in adolescent Menière's disease (MD). Methods: The medical records of adolescents with MD (11-17 years old) from May 2014 to March 2023 in Shandong Provincial ENT Hospital were retrospectively analyzed, including clinical features, a battery of auditory and vestibular function tests, sensory organization test, and imaging assessments. Patients with recurrent vertigo of childhood (RVC) were as controls. Results: Compared with RVC, adolescent MD showed higher pure tone average threshold (p < .001), lower speech discrimination score (p = .014), and lower otoacoustic emission pass rates (p = .005). Adolescents with MD exhibited significant reduction in equilibrium score (Conditions 1, 5, and 6; p1 = .035; p5 = .033; p6 = .003), composite sensory score (p = .014), and vestibular sensory score (p = .029). Adolescents with bilateral MD exhibited worse performance in equilibrium score and strategy score compared to adolescents with unilateral MD. For the affected ear, the more severe endolymphatic hydrops detected by gadolinium-enhanced magnetic resonance imaging, the higher the auditory brainstem response threshold (r = .850, p = .007), and the lower the otoacoustic emission pass rate (r = -.976, p < .001). Conclusion: Adolescent MD has similar vestibular information inputs with that of RVC, but the ability for the nerve center to use these clues to maintain balance is worse in adolescents with MD. There were potential differences in vestibular weights in adolescents with unilateral and bilateral MD, also potential effects on vision and proprioception. Level of Evidence: Level 4.

12.
Laryngoscope ; 133(7): 1734-1736, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-36815612

RESUMO

There is currently no satisfactory treatment for otolith dysfunctions. Here, we propose a novel surgical method, vestibule plugging (VP), and the results confirm its effectiveness and safety in treatment of otolith dysfunction. Laryngoscope, 133:1734-1736, 2023.


Assuntos
Membrana dos Otólitos , Vestíbulo do Labirinto , Humanos
13.
Clin Exp Med ; 23(7): 3361-3371, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37743423

RESUMO

The etiology of Ménière's disease (MD) remains controversial. Allergies are potential extrinsic factors that, in conjunction with underlying intrinsic factors, may cause MD. The link between allergies and MD was first described in 1923. For nearly a century, studies have demonstrated a possible link between allergies and MD, even though a causal relationship has not been definitively determined. Previous reviews have mainly focused on clinical epidemiology studies of patients. In this review, we shed light on the association between allergies and MD not only in terms of its epidemiology, but also from an immunology, pathophysiology, and immunotherapy perspective in both patients and animal models. Patients with MD tend to have a high risk of comorbid allergies or an allergy history, showing positive allergy immunology characteristics. Other MD-related diseases, such as migraine, may also interact with allergies. Allergy mediators such as IgE may worsen the symptoms of MD. Deposits of IgE in the vestibular end organs indicate the ability of the inner ear to participate in immune reactions. Allergic challenges can induce vertigo in animals and humans. Anti-allergy therapy plays a positive role in patients with MD and animal models of endolymphatic hydrops.


Assuntos
Hidropisia Endolinfática , Hipersensibilidade , Doença de Meniere , Animais , Humanos , Doença de Meniere/epidemiologia , Doença de Meniere/etiologia , Doença de Meniere/terapia , Hidropisia Endolinfática/diagnóstico , Hidropisia Endolinfática/etiologia , Hipersensibilidade/epidemiologia , Hipersensibilidade/terapia , Hipersensibilidade/complicações , Imunoterapia , Imunoglobulina E
14.
Laryngoscope ; 133(11): 3178-3184, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37036082

RESUMO

OBJECTIVES: The study goals were to compare the long-term efficacy of semicircular canal plugging (SCP) with labyrinthectomy in the treatment of advanced Meniere's disease (MD). STUDY DESIGN: A retrospective study. SETTING: Single tertiary medical center. METHODS: A total of 116 MD patients (TSCP group of 90; labyrinthectomy group of 26) with complete medical documents in Shandong Provincial ENT Hospital, from March 2017 to March 2019 were retrospectively analyzed, including a battery of auditory and vestibular function tests, recovery time from imbalance and function level scores (FLS). RESULTS: The total control rate of vertigo in the TSCP group was 96.7% (87/90). The rate of hearing loss was 23.3% (21/90). The control rate of vertigo in the labyrinthectomy group was 100% (26/26). All patients lost their auditory function after labyrinthectomy with a 100% hearing loss rate. There was no significant difference in the vertigo control rate between the two groups (P > 0.05). The hearing loss rate in the TSCP group was significantly lower than that in the labyrinthectomy group (P < 0.00). The median time recovered from imbalance was 15 days in TSCP group and 21 days in labyrinthectomy group, which is significantly different (P < 0.05). There was no significant difference in the FLS between the two groups (P > 0.05). CONCLUSIONS: Compared to labyrinthectomy, TSCP can preserve hearing at a high probability; meanwhile, otolith organ function preservation benefits patients from faster vestibular compensation. LEVEL OF EVIDENCE: 3 Laryngoscope, 133:3178-3184, 2023.


Assuntos
Surdez , Perda Auditiva , Doença de Meniere , Humanos , Doença de Meniere/cirurgia , Estudos Retrospectivos , Canais Semicirculares/cirurgia , Vertigem/etiologia , Vertigem/cirurgia
15.
Nat Commun ; 14(1): 1249, 2023 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-36872329

RESUMO

Ménière's disease, a multifactorial disorder of the inner ear, is characterized by severe vertigo episodes and hearing loss. Although the role of immune responses in Ménière's disease has been proposed, the precise mechanisms remain undefined. Here, we show that downregulation of serum/glucocorticoid-inducible kinase 1 is associated with activation of NLRP3 inflammasome in vestibular-resident macrophage-like cells from Ménière's disease patients. Serum/glucocorticoid-inducible kinase 1 depletion markedly enhances IL-1ß production which leads to the damage of inner ear hair cells and vestibular nerve. Mechanistically, serum/glucocorticoid-inducible kinase 1 binds to the PYD domain of NLRP3 and phosphorylates it at Serine 5, thereby interfering inflammasome assembly. Sgk-/- mice show aggravated audiovestibular symptoms and enhanced inflammasome activation in lipopolysaccharide-induced endolymphatic hydrops model, which is ameliorated by blocking NLRP3. Pharmacological inhibition of serum/glucocorticoid-inducible kinase 1 increases the disease severity in vivo. Our studies demonstrate that serum/glucocorticoid-inducible kinase 1 functions as a physiologic inhibitor of NLRP3 inflammasome activation and maintains inner ear immune homeostasis, reciprocally participating in models of Ménière's disease pathogenesis.


Assuntos
Hidropisia Endolinfática , Doença de Meniere , Animais , Camundongos , Glucocorticoides , Inflamassomos , Proteína 3 que Contém Domínio de Pirina da Família NLR , Macrófagos
16.
Artigo em Inglês | MEDLINE | ID: mdl-22085972

RESUMO

AIM: Vestibular hair cell loss in response to different stimuli may be attributable to the occurrence of apoptosis, in which apoptosis-inducing factor (AIF) is an important regulator mediating apoptotic process independent of caspases. This study was designed to investigate the possible involvement of AIF in gentamicin (GM)-induced vestibular hair cell death. METHODS: Vestibular organs from postnatal day 3 or 4 rats were maintained in tissue culture and were exposed to 2 mg/ml GM for up to 72 h. Vestibular hair cell viability was quantified by MTT assay. Apoptosis was determined by flow cytometry. AIF activation was examined by RT-PCR. The expressions of the mitochondrial protein and cytoplasm protein of AIF were detected by Western blot. RESULTS: GM could significantly inhibit the cell viability of vestibular hair cells in a dose- and time-dependent manner. The number of apoptotic cells treated with GM was higher than that of cells not treated with GM. RT-PCR showed upregulation of AIF mRNA under GM. Western blot showed that AIF from mitochondria was decreased, whereas AIF from cytoplasm was increased after GM exposure. CONCLUSIONS: AIF participates in GM-induced apoptosis of vestibular hair cells.


Assuntos
Fator de Indução de Apoptose/genética , Apoptose/fisiologia , Regulação da Expressão Gênica no Desenvolvimento , Células Ciliadas Vestibulares/patologia , RNA Mensageiro/genética , Vestíbulo do Labirinto/patologia , Animais , Animais Recém-Nascidos , Apoptose/efeitos dos fármacos , Fator de Indução de Apoptose/biossíntese , Western Blotting , Sobrevivência Celular , Células Cultivadas , Modelos Animais de Doenças , Citometria de Fluxo , Gentamicinas/toxicidade , Células Ciliadas Vestibulares/efeitos dos fármacos , Células Ciliadas Vestibulares/metabolismo , Ratos , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/metabolismo
17.
Front Neurol ; 13: 827462, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35359640

RESUMO

Background: To explore the long-term efficacy and safety of resection of the lateral wall of the endolymphatic sac for the treatment of intractable Meniere's disease (MD) as an alternative surgical procedure for treating this disorder. Methods: Data from 73 patients who were referred to our hospital and diagnosed with unilateral MD between January 2015 and June 2019 were retrospectively analyzed in this study. Seventy-three patients who had frequent vertigo even after receiving standardized conservative treatment for at least half a year underwent resection of the lateral wall of the endolymphatic sac. Vertigo control and auditory function were assessed. Pure tone audiometry, caloric test, and vestibular evoked myogenic potential were performed to evaluate audiological and vestibular functions. The post-operative follow-up duration was more than 2 years. Results: Among the 73 patients (male 34 cases, female 39 cases; age 20-69 years, average 51.4), vertigo was controlled effectively for 66 cases (90.4%) after 2 years of follow-up; 45 cases (61.6%) were completely controlled, and 21 cases (28.8%) were substantially controlled in this study. The patients of 16.4% had hearing loss with more than 10 dB change based on the four-tone average (0.5, 1, 2 and 3 kHz). No patient had a facial nerve weakness, cerebrospinal fluid leakage, or other complications. Conclusion: Resection of the lateral wall of the endolymphatic sac, which can effectively control vertiginous symptoms in intractable MD patients, represents an effective and safe therapy for this disease. Resection of the lateral wall of the endolymphatic sac is expected to be used as an alternative treatment for MD.

18.
Appl Biochem Biotechnol ; 194(8): 3483-3493, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35366186

RESUMO

Herpes simplex virus type 1 (HSV-1) results in the development of Bell's pals but still, the pathophysiology of the facial nerve paralysis is still not fully studied. The main objective is to establish an animal model of type 1 herpes simplex virus (HSV-1)-induced face paralysis in the mouse and to investigate the pattern of changes in intercellular adhesion molecule -1(ICAM-1) expression in the facial nucleus of the brain stem in mice with facial paralysis as well as the effects of glucocorticoids on intercellular adhesion molecule -1(ICAM-1) expression. A total of 170 4-week-old Balb/c male mice were randomly divided into the virus inoculation group (n = 135), saline control group (n = 26), and blank control group (n = 9). Mice in the virus inoculation group that showed facial paralysis were divided into A, B, and C subgroups. The A group did not receive any treatments, the B group received methylprednisolone sodium succinate (MPSS) intervention, and the C group received MPSS + RU486 treatment. The mouse model of facial paralysis was established by inoculating HSV-1 to the skin at the back of the ears. The facial nerve function of mice was assessed, and real-time PCR and western blot were used to assess ICAM-1 expression in the facial nucleus of the brain stem in mice with facial paralysis after drug intervention. In the virus inoculation group, 95 mice (55.88%) showed varying degrees of facial paralysis symptoms within 2-5 days after inoculation. The ICAM-1 gene and protein expression levels remained at low levels in the facial nucleus of the brain stem of mice in the saline group, which showed no significant difference compared to the normal control group (P > 0.05). However, for mice of the virus inoculation group, ICAM-1 expression increased at 6 h after the occurrence of facial paralysis and peaked after 2 days, differing significantly from the blank control group (P < 0.01). ICAM-1 expression subsequently decreased gradually. In the HSV-1 + MPSS group, ICAM-1 protein expression decreased significantly on the 2nd day after facial paralysis. In the HSV-1 + MPSS + RU486 group, MPSS inhibition of ICAM-1 protein expression was reduced. The results suggested that ICAM-1 is involved in the pathological processes by which HSV-1 induces facial paralysis in mice, and the treatment effects of MPSS for Bell's palsy can be achieved by the inhibition of MCP-1.


Assuntos
Paralisia de Bell , Paralisia Facial , Herpesvirus Humano 1 , Animais , Paralisia de Bell/metabolismo , Tronco Encefálico/metabolismo , Tronco Encefálico/patologia , Modelos Animais de Doenças , Paralisia Facial/tratamento farmacológico , Paralisia Facial/metabolismo , Paralisia Facial/patologia , Molécula 1 de Adesão Intercelular/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Mifepristona/metabolismo
19.
Front Psychol ; 13: 818967, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35401359

RESUMO

Objective: This study aimed to analyze the hearing improvement and prognosis factors of idiopathic sudden sensorineural hearing loss (ISSNHL) in different ages with initial total hearing loss. Methods: We reviewed the medical records of 5,711 hospitalized patients with ISSNHL from 2016 to 2021 in our center. All of the patients had been treated with uniform combination drug therapy. After excluding the patients with initial partial hearing loss and those diagnosed with clear etiology, 188 patients were enrolled in this study and divided into six age groups (18-30, 31-40, 41-50, 51-60, 61-70, ≥ 71 years). In all groups, decreases in pure-tone average (PTA) 1 month posttreatment, effective rate, and clinical characteristics (vertigo, tinnitus, hospital stay, comorbidity, and inner ear magnetic resonance imaging) were analyzed. Results: Among the 188 enrolled patients, 86% had vertigo. Complete recovery was seen in 0.5% of patients, and marked recovery was seen in 43% of patients. The mean 1 month posttreatment PTAs were as follows: 18-30 years: 80 ± 7.5 dB; 31-40 years: 100 ± 9.0 dB; 41-50 years: 99 ± 8.3 dB; 51-60 years: 101 ± 8.6 dB; 61-70 years: 96 ± 9.6 dB; and ≥ 71 years: 88 ± 13.0 dB. Compared with the other groups, the 18-30- years group showed better recovery of hearing threshold in five frequencies (0.25, 0.5, 1, 2, and 4 kHz, respectively, at octave or semioctave frequencies under air conduction), and the recovery of hearing threshold at 0.25 and 0.5 Hz was better than the recovery at 1, 2, and 4 kHz. According to the results of the chi-square test statistical analysis, vertigo and comorbidities were associated with a poor prognosis of ISSNHL. Conclusion: In summary, the treatment outcomes of patients with ISSNHL with initial total hearing loss were poor. There was a significant age-related difference with respect to marked recovery 1 month posttreatment, and the 18-30- years group showed better recovery than the other age groups.

20.
Front Neurol ; 13: 970610, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36425799

RESUMO

Background: Migraine plays an important role in some subgroups of children with recurrent vertigo. Moreover, the migraine component varies from definite to possibly absent as defined in this spectrum of three disorders-vestibular migraine of childhood (VMC), probable VMC (pVMC), and recurrent vertigo of childhood (RVC). However, studies on the sensory organization of balance control in these three disorders are rare. Objective: To explore the balance control of children with RVC, VMC, and pVMC, when the three sensory systems are challenged. Method: A retrospective analysis was performed on 125 children with VMC (18 female and 15 male; aged 11.64 ± 2.74), pVMC (10 female and eight male; aged 11.78 ± 2.51), and RVC (32 female and 42 male; aged 11.10 ± 2.60). All children in each subtype were divided into groups of children aged ≤ 12 years old and 13-17 years old. Vestibular examination screening and assessment for postural control using the six conditions of the sensory organization test (SOT) were performed. The three primary outcome measures were: equilibrium score (ES), strategy score (SS), and sensory analysis score of the SOT. Results: Equilibrium score under six different conditions and composite score increased with age (all P-values < 0.05). The somatosensory and visual scores also improved with growing (P-values < 0.05). However, vestibular scores did not increase significantly with age as the other senses did (P > 0.05). In the children ≤ 12 year-old group, children with VMC had a significantly higher visual preference score than those with pVMC and RVC (P < 0.05). There was an effect of age on the horizontal HIT. Ocular vestibular evoked myogenic potential (oVEMP), cervical vestibular evoked myogenic potential (cVEMP), and unilateral weakness (UW) values showed no significant difference among three diseases. Conclusion: Compared with patients at the age of 13-17 years old and with RVC and pVMC (both ≤ 12 years old), children with VMC had a higher degree of reliance on visual signals to maintain their balance and a poorer central integration of peripheral information before reaching 12 years of age. In addition, vision may predominate by weakening vestibular function based on visuo-vestibular interactions. It must be noted that peripheral vestibular examinations could not distinguish the three disease subtypes.

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