Background: Changes in the gene expressions for tumor necrosis factor-α (TNF-α) and/or interleukin-1β (IL-1β) during tinnitus have not been previously reported. We evaluated tinnitus and mRNA expression levels of TNF-α, IL-1β, and N-methyl D-aspartate receptor subunit 2B (NR2B) genes in cochlea and inferior colliculus (IC) of mice after intraperitoneal injections of salicylate. Methods: Forty-eight 3-month-old male SAMP8 mice were randomly and equally divided into two groups: salicylate-treated and saline-treated. All mice were trained to perform an active avoidance task for 5 days. Once conditioned, an active avoidance task was performed 2 hours after daily intraperitoneal injections of saline, either alone or containing 300 mg/kg sodium salicylate. Total numbers of times (tinnitus score) the mice climbed during the inter-trial silent period for 10 trials were recorded daily for 4 days (days 7 to 10), and then mice were euthanized for determination of mRNA expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC at day 10. Results: Tinnitus scores increased in response to daily salicylate treatments. The mRNA expression levels of TNF-α increased significantly for the salicylate-treated group compared to the control group in both cochlea (1.89 ± 0.22 vs. 0.87 ± 0.07, P < 0.0001) and IC (2.12 ± 0.23 vs. 1.73 ± 0.22, p = 0.0040). mRNA expression levels for the IL-1β gene also increased significantly in the salicylate group compared to the control group in both cochlea (3.50 ± 1.05 vs. 2.80 ± 0.28, p < 0.0001) and IC (2.94 ± 0.51 versus 1.24 ± 0.52, p = 0.0013). Linear regression analysis revealed a significant positive association between tinnitus scores and expression levels of TNF-α, IL-1β, and NR2B genes in cochlea and IC. In addition, expression levels of the TNF-α gene were positively correlated with those of the NR2Bgene in both cochlea and IC; whereas, the expression levels of the IL-1β gene was positively correlated with that of the NR2B gene in IC, but not in cochlea. Conclusion: We conclude that salicylate treatment resulting in tinnitus augments expression of the TNF-α and IL-1β genes in cochlea and IC of mice, and we suggest that these proinflammatory cytokines might lead to tinnitus directly or via modulating the NMDA receptor.
22 July 2018 in Annals of Otology, Rhinology & Laryngology
Objectives: Vestibular schwannomas, also known as acoustic neuromas, are slow-growing tumors that may lead to asymmetric hearing loss, unilateral tinnitus, and vertigo. Population-based data are lacking regarding the incidence of vestibular schwannoma in Asian populations. The aim of this study was to investigate the incidence of vestibular schwannoma in Taiwan using data from a population-based health claim database. Subjects and Methods: Patients aged 20 years and over with incident cases of vestibular schwannoma between January 1, 2001, and December 31, 2012, were identified from the Longitudinal Health Insurance Database 2000 of the National Health Insurance Research Database (NHIRD), Taiwan, based on the International Classification of Diseases, 9th Revision, Clinical Modification (ICD-9-CM) code 225.1. Only those patients who had received a magnetic resonance imaging scan prior to the diagnosis of vestibular schwannoma were considered as definitive cases. Results: 206 cases of vestibular schwannoma were identified during the interval 2001 to 2012. The overall annual incidence was 2.66 per 100 000 persons (95% confidence interval, 2.32-3.05). The annual incidence rate varied throughout the study period, ranging from 1.74 to 3.72 per 100 000 persons. The highest incidence rate of 4.86 per 100 000 persons was observed in the age group of 60 to 69 years. Conclusions: Based on data from the NHIRD in Taiwan for the years 2001 to 2012, the average annual incidence rate of vestibular schwannoma was found to be 2.66 per 100 000 persons.
Tinnitus and ischemic cerebrovascular disease (ICVD) may share common pathophysiologic mechanisms. Nevertheless, no studies have investigated whether tinnitus is associated with a higher risk of ICVD. The aim of this study was to evaluate the risk of ICVD among young and middle-aged patients with tinnitus. Using the Taiwan’s National Health Insurance Research Database, we identified 3,474 patients 20–45 years old with incident ICVD diagnosed between January 1, 2000 and December 31, 2010 and 17,370 controls, frequency matched on age interval, sex, and year of the index date. Risk of ICVD associated with tinnitus was assessed using multiple logistic regression analyses. Tinnitus was significantly associated with a higher risk of incident ICVD among young and middle-aged patients (adjusted odds ratio [OR] 1.66, 95% confidence interval [CI] 1.34–2.04), adjusting for sex, age, and comorbidities. In addition, sex-stratified analysis showed that the associations were significant in both male (adjusted OR 1.55, 95% CI 1.16–2.07) and female patients (adjusted OR 1.77, 95% CI 1.30–2.41). Furthermore, tinnitus was significantly associated with a higher risk of ICVD in the 20.0–29.9 years (adjusted OR 4.11, 95% CI 1.98–8.52) and 30.0–39.9 years (adjusted OR 2.19, 95% CI 1.57–3.05) age groups, but not in the 40.0–45.0 years age group. Tinnitus could be a novel risk factor or clinical indicator for young ischemic stroke, and further investigations are warranted.