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Hearing Research Jun 2024Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual...
Following adult-onset hearing impairment, crossmodal plasticity can occur within various sensory cortices, often characterized by increased neural responses to visual stimulation in not only the auditory cortex, but also in the visual and audiovisual cortices. In the present study, we used an established model of loud noise exposure in rats to examine, for the first time, whether the crossmodal plasticity in the audiovisual cortex that occurs following a relatively mild degree of hearing loss emerges solely from altered intracortical processing or if thalamocortical changes also contribute to the crossmodal effects. Using a combination of an established pharmacological 'cortical silencing' protocol and current source density analysis of the laminar activity recorded across the layers of the audiovisual cortex (i.e., the lateral extrastriate visual cortex, V2L), we observed layer-specific changes post-silencing in the strength of the residual visual, but not auditory, input in the noise exposed rats with mild hearing loss compared to rats with normal hearing. Furthermore, based on a comparison of the laminar profiles pre- versus post-silencing in both groups, we can conclude that noise exposure caused a re-allocation of the strength of visual inputs across the layers of the V2L cortex, including enhanced visual-evoked activity in the granular layer; findings consistent with thalamocortical plasticity. Finally, we confirmed that audiovisual integration within the V2L cortex depends on intact processing within intracortical circuits, and that this form of multisensory processing is vulnerable to disruption by noise-induced hearing loss. Ultimately, the present study furthers our understanding of the contribution of intracortical and thalamocortical processing to crossmodal plasticity as well as to audiovisual integration under both normal and mildly-impaired hearing conditions.
PubMed: 38941694
DOI: 10.1016/j.heares.2024.109071 -
Pharmaceuticals (Basel, Switzerland) Jun 2024Hearing loss is one of the most common types of disability; however, there is only one FDA-approved drug to prevent any type of hearing loss. Treatment with the highly...
Hearing loss is one of the most common types of disability; however, there is only one FDA-approved drug to prevent any type of hearing loss. Treatment with the highly effective chemotherapy agent, cisplatin, and exposure to high-decibel noises are two of the most common causes of hearing loss. The mitogen-activated protein kinase (MAPK) pathway, a phosphorylation cascade consisting of RAF, MEK1/2, and ERK1/2, has been implicated in both types of hearing loss. Pharmacologically inhibiting BRAF or ERK1/2 is protective against noise- and cisplatin-induced hearing loss in multiple mouse models. Trametinib, a MEK1/2 inhibitor, protects from cisplatin-induced outer hair cell death in mouse cochlear explants; however, to the best of our knowledge, inhibiting MEK1/2 has not yet been shown to be protective against hearing loss in vivo. In this study, we demonstrate that trametinib protects against cisplatin-induced hearing loss in a translationally relevant mouse model and does not interfere with cisplatin's tumor-killing efficacy in cancer cell lines. Higher doses of trametinib were toxic to mice when combined with cisplatin, but lower doses of the drug were protective against hearing loss without any known toxicity. Trametinib also protected mice from noise-induced hearing loss and synaptic damage. This study shows that MEK1/2 inhibition protects against both insults of hearing loss, as well as that targeting all three kinases in the MAPK pathway protects mice from cisplatin- and noise-induced hearing loss.
PubMed: 38931403
DOI: 10.3390/ph17060735 -
Micromachines Jun 2024Certain ocular conditions result from the non-physiological presence of intraocular particles, leading to visual impairment and potential long-term damage. This happens...
Certain ocular conditions result from the non-physiological presence of intraocular particles, leading to visual impairment and potential long-term damage. This happens when the normally clear aqueous humor becomes less transparent, thus blocking the visual axis and by intraocular pressure elevation due to blockage of the trabecular meshwork, as seen in secondary open-angle glaucoma (SOAG). Some of these "particle-related pathologies" acquire ocular conditions like pigment dispersion syndrome, pseodoexfoliation and uveitis. Others are trauma-related, such as blood cell accumulation in hyphema. While medical and surgical treatments exist for SOAG, there is a notable absence of effective preventive measures. Consequently, the prevailing clinical approach predominantly adopts a "wait and see" strategy, wherein the focus lies on managing secondary complications and offers no treatment options for particulate matter disposal. We developed a new technique utilizing standing acoustic waves to trap and direct intraocular particles. By employing acoustic trapping at nodal regions and controlled movement of the acoustic transducer, we successfully directed these particles to specific locations within the angle. Here, we demonstrate control and movement of polystyrene (PS) particles to specific locations within an in vitro eye model, as well as blood cells in porcine eyes (ex vivo). The removal of particles from certain areas can facilitate the outflow of aqueous humor (AH) and help maintain optimal intraocular pressure (IOP) levels, resulting in a non-invasive tool for preventing secondary glaucoma. Furthermore, by controlling the location of trapped particles we can hasten the clearance of the AH and improve visual acuity and quality more effectively. This study represents a significant step towards the practical application of our technique in clinical use.
PubMed: 38930756
DOI: 10.3390/mi15060786 -
International Journal of Molecular... Jun 2024Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to...
Noise-induced hearing loss (NIHL) is a major cause of hearing impairment and is linked to dementia and mental health conditions, yet no FDA-approved drugs exist to prevent it. Downregulating the mitogen-activated protein kinase (MAPK) cellular pathway has emerged as a promising approach to attenuate NIHL, but the molecular targets and the mechanism of protection are not fully understood. Here, we tested specifically the role of the kinases ERK1/2 in noise otoprotection using a newly developed, highly specific ERK1/2 inhibitor, tizaterkib, in preclinical animal models. Tizaterkib is currently being tested in phase 1 clinical trials for cancer treatment and has high oral bioavailability and low predicted systemic toxicity in mice and humans. In this study, we performed dose-response measurements of tizaterkib's efficacy against permanent NIHL in adult FVB/NJ mice, and its minimum effective dose (0.5 mg/kg/bw), therapeutic index (>50), and window of opportunity (<48 h) were determined. The drug, administered orally twice daily for 3 days, 24 h after 2 h of 100 dB or 106 dB SPL noise exposure, at a dose equivalent to what is prescribed currently for humans in clinical trials, conferred an average protection of 20-25 dB SPL in both female and male mice. The drug shielded mice from the noise-induced synaptic damage which occurs following loud noise exposure. Equally interesting, tizaterkib was shown to decrease the number of CD45- and CD68-positive immune cells in the mouse cochlea following noise exposure. This study suggests that repurposing tizaterkib and the ERK1/2 kinases' inhibition could be a promising strategy for the treatment of NIHL.
Topics: Animals; Mice; Administration, Oral; Hearing Loss, Noise-Induced; Male; Protein Kinase Inhibitors; MAP Kinase Signaling System; Female; Disease Models, Animal; Cochlea
PubMed: 38928015
DOI: 10.3390/ijms25126305 -
Journal of the Association For Research... Jun 2024Transient receptor potential (TRP) channels play key roles in sensory biology as transducers of various stimuli. Although these ion channels are expressed in the...
Transient receptor potential (TRP) channels play key roles in sensory biology as transducers of various stimuli. Although these ion channels are expressed in the cochlea, their functions remain poorly understood. Recent studies by Vélez-Ortega and colleagues indicate that their expression by non-sensory supporting cells helps limit damage from acoustic trauma.
PubMed: 38926267
DOI: 10.1007/s10162-024-00954-1 -
Proteomes Jun 2024Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult... (Review)
Review
Characterising inner ear disorders represents a significant challenge due to a lack of reliable experimental procedures and identified biomarkers. It is also difficult to access the complex microenvironments of the inner ear and investigate specific pathological indicators through conventional techniques. Omics technologies have the potential to play a vital role in revolutionising the diagnosis of ear disorders by providing a comprehensive understanding of biological systems at various molecular levels. These approaches reveal valuable information about biomolecular signatures within the cochlear tissue or fluids such as the perilymphatic and endolymphatic fluid. Proteomics identifies changes in protein abundance, while metabolomics explores metabolic products and pathways, aiding the characterisation and early diagnosis of diseases. Although there are different methods for identifying and quantifying biomolecules, mass spectrometry, as part of proteomics and metabolomics analysis, could be utilised as an effective instrument for understanding different inner ear disorders. This study aims to review the literature on the application of proteomic and metabolomic approaches by specifically focusing on Meniere's disease, ototoxicity, noise-induced hearing loss, and vestibular schwannoma. Determining potential protein and metabolite biomarkers may be helpful for the diagnosis and treatment of inner ear problems.
PubMed: 38921823
DOI: 10.3390/proteomes12020017 -
Current Neurovascular Research Jun 2024Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing...
BACKGROUND
Adherens junction in the blood-labyrinth barrier is largely unexplored because it is traditionally thought to be less important than the tight junction. Since increasing evidence indicates that it actually functions upstream of tight junction adherens junction may potentially be a better target for ameliorating the leakage of the blood-labyrinth barrier under pathological conditions such as acoustic trauma.
AIMS
This study was conducted to investigate the pathogenesis of the disruption of adherens junction after acoustic trauma and explore potential therapeutic targets.
METHODS
Critical targets that regulated the disruption of adherens junction were investigated by techniques such as immunofluorescence and Western blottingin C57BL/6J mice.
RESULTS
Upregulation of Vascular Endothelial Growth Factor (VEGF) and downregulation of Pigment Epithelium-derived Factor (PEDF) coactivated VEGF-PEDF/VEGF receptor 2 (VEGFR2) signaling pathway in the stria vascularis after noise exposure. Downstream effector Src kinase was then activated to degrade VE-cadherin and dissociate adherens junction which led to the leakage of the blood-labyrinth barrier. By inhibiting VEGFR2 or Src kinase VE-cadherin degradation and blood-labyrinth barrier leakage could be attenuated but Src kinase represented a better target to ameliorate blood-labyrinth barrier leakage as inhibiting it would not interfere with vascular endothelium repair neurotrophy and pericytes proliferation mediated by upstream VEGFR2.
CONCLUSION
Src kinase may represent a promising target to relieve noise-induced disruption of adherens junction and hyperpermeability of the blood-labyrinth barrier.
PubMed: 38918992
DOI: 10.2174/0115672026320884240620070951 -
Asian Pacific Journal of Cancer... Jun 2024Exposure to noise by generation of free radicals causes oxidative stress in body. The aim of this study was the evaluation of oxidative stress in workers who have used...
BACKGROUND AND OBJECTIVE
Exposure to noise by generation of free radicals causes oxidative stress in body. The aim of this study was the evaluation of oxidative stress in workers who have used hearing protection devices during working time.
MATERIAL AND METHOD
Pressing workers (n=24) of a home appliance industry were studied using hearing protection devices to reduce noise exposure. Twenty two office staff (without exposure to noise) were considered as a control group. Two groups were matched for age, work experience and smoking. Exposure to noise was measured by dosimeter method at workstations. By obtaining 3 ml blood sample, Malondialdehyde levels, Thiol groups and total antioxidant capacity were evaluated in all subjects.
RESULTS
Exposure to sound pressure level in pressing workers by considering the noise reduction factor of the earplug was observed in 77.65 dB with minimum 75.1 dB and Maximum 81.22 dB. Plasma thiol groups (0.076 (0.041-0.119) vs (0.110 (0.076-0.197), mmol/l P =0.0001) and total antioxidant capacity (361.33± 54.65 vs 414.14± 96.82, µmol/ml P = 0.026) in pressing workers significantly decreased than control group. Pearson correlation showed significant results between exposure to noise and oxidative stress parameters.
CONCLUSION
Exposure to noise wave cause oxidative stress in different site of body. Oxidative stress is an intermediate way for different disease due to noise exposure. Reducing of noise exposure by earplug in pressing workers is not efficient protection for oxidative stress generation. Therefore, hearing protection devices are not a barrier to the harmful effects of noise in occupational exposure.
Topics: Humans; Oxidative Stress; Occupational Exposure; Adult; Male; Noise, Occupational; Case-Control Studies; Ear Protective Devices; Hearing Loss, Noise-Induced; Antioxidants; Middle Aged; Follow-Up Studies; Malondialdehyde; Female; Occupational Diseases; Industry; Prognosis
PubMed: 38918653
DOI: 10.31557/APJCP.2024.25.6.1929 -
PloS One 2024This study aimed to understand the health of workers exposed to occupational noise and explore the influencing factors related to workers' health, especially the impact...
OBJECTIVE
This study aimed to understand the health of workers exposed to occupational noise and explore the influencing factors related to workers' health, especially the impact of noise on workers' hearing. This work can provide a basis for formulating relevant measures for occupational noise prevention and control in the future.
METHODS
On the basis of the key occupational disease monitoring project in Chongqing, China, in 2021, the data of 1125 workers exposed to occupational noise were analyzed. Data included demographic information, occupational history, clinical physical examination information, and noise detection information of the working environment. Chi-square test and multifactorial logistic regression were used for statistical analysis.
RESULTS
The prevalence rates of abnormal electrocardiogram (ECG), blood pressure (BP), and pure tone audiometry (PTA) were 21.9% (246/1125), 27.8% (313/1125), and 18.0% (202/1125), respectively. Male workers accounted for 78.8%. Compared with male workers, female workers had a lower prevalence of abnormal PTA (OR = 0.28, 95% CI = 0.16-0.50). Workers working in medium enterprises had a lower prevalence of abnormal BP than workers in micro enterprises (OR = 0.36, 95% CI = 0.19-0.66). The prevalence of abnormal BP and PTA of workers increased with age. After adjusting for age, sex, and body mass index, the prevalence of abnormal ECG of mining workers was higher than that of manufacturing workers (OR = 1.54, 95% CI = 1.07-2.24), and the prevalence of abnormal PTA had a rising trend with the increase in noise exposure value.
CONCLUSION
Noise-exposed workers have a high prevalence of abnormal ECG, BP, and PTA, and factors such as age, enterprise size, and workplace noise exposure are correlated with the aberrant health of workers. Governments, enterprises, and individuals need to attach great importance to the possible adverse effects of noise. They must also actively adopt various effective measures to protect the occupational safety and health of workers.
Topics: Humans; Noise, Occupational; Male; China; Female; Cross-Sectional Studies; Adult; Middle Aged; Occupational Exposure; Prevalence; Hearing Loss, Noise-Induced; Blood Pressure; Occupational Diseases; Electrocardiography; Audiometry, Pure-Tone; Young Adult
PubMed: 38917109
DOI: 10.1371/journal.pone.0305576 -
The Journal of Head Trauma... Jun 2024We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but...
OBJECTIVES
We investigated the acoustic startle reflex in recently concussed adolescent athletes compared to healthy controls and those with concussion history (>1 year prior) but no current symptoms. We hypothesized that individuals with recent concussion would have a suppressed startle response compared to healthy controls.
METHODS
We conducted a cross-sectional study on 49 adolescent athletes with a recent concussion (n = 20; age: 14.6 ± 1.6 years; 60% female), a concussion history > 1 year prior (n = 16; age: 14.8 ± 2.0 years; 44% female), and healthy controls (n = 13; age: 13.3 ± 2.8 years; 54% female). We measured the eyeblink of the general startle reflex via electromyography activity of the orbicularis oculi muscle using electrodes placed under the right eye. Measurement sessions included twelve 103 decibel acoustic startle probes ~50 milliseconds in duration delivered ~15-25 seconds apart. The primary dependent variable was mean startle magnitude (µV), and group was the primary independent variable. We used a one-way analysis of variance followed by a Tukey post hoc test to compare mean startle magnitude between groups.
RESULTS
Mean startle magnitude significantly differed (F = 5.49, P = .007) among the groups. Mean startle magnitude was significantly suppressed for the concussion (P = .01) and concussion history groups (P = .02) compared to healthy controls. There was no significant difference between the recent concussion and concussion history groups (P = 1.00).
CONCLUSION
Our results provide novel evidence for startle suppression in adolescent athletes following concussion. The concussion history group had an attenuated startle response beyond resolution of their recovery, suggesting there may be lingering physiological dysfunction.
PubMed: 38916433
DOI: 10.1097/HTR.0000000000000979