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Nature Reviews. Disease Primers Jan 2017Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries,... (Review)
Review
Congenital hearing loss (hearing loss that is present at birth) is one of the most prevalent chronic conditions in children. In the majority of developed countries, neonatal hearing screening programmes enable early detection; early intervention will prevent delays in speech and language development and has long-lasting beneficial effects on social and emotional development and quality of life. A diagnosis of hearing loss is usually followed by a search for an underlying aetiology. Congenital hearing loss might be attributed to environmental and prenatal factors, which prevail in low-income settings; congenital infections, particularly cytomegalovirus infection, are also a common risk factor for hearing loss. Genetic causes probably account for the majority of cases in developed countries; mutations can affect any component of the hearing pathway, in particular, inner ear homeostasis (endolymph production and maintenance) and mechano-electrical transduction (the conversion of a mechanical stimulus into electrochemical activity). Once the underlying cause of hearing loss is established, it might direct therapeutic decision making and guide prevention and (genetic) counselling. Management options include specific antimicrobial therapies, surgical treatment of craniofacial abnormalities and implantable or non-implantable hearing devices. An improved understanding of the pathophysiology and molecular mechanisms that underlie hearing loss and increased awareness of recent advances in genetic testing will promote the development of new treatment and screening strategies.
Topics: Animals; Hearing Loss; Humans; Infant, Newborn; Risk Factors
PubMed: 28079113
DOI: 10.1038/nrdp.2016.94 -
CMAJ : Canadian Medical Association... Sep 2003There is compelling evidence that free-floating endolymph particles in the posterior semicircular canal underlie most cases of benign paroxysmal positional vertigo... (Review)
Review
There is compelling evidence that free-floating endolymph particles in the posterior semicircular canal underlie most cases of benign paroxysmal positional vertigo (BPPV). Recent pathological findings suggest that these particles are otoconia, probably displaced from the otolithic membrane in the utricle. They typically settle in the dependent posterior canal and render it sensitive to gravity. Well over 90% of patients can be successfully treated with a simple outpatient manoeuvre that moves the particles back into the utricle. We describe the various techniques for this manoeuvre, plus treatments for uncommon variants of BPPV such as that of the lateral canal. For the rare patient whose BPPV is not responsive to these manoeuvres and has severe symptoms, posterior canal occlusion surgery is a safe and highly effective procedure.
Topics: Aged; Ear, Inner; Female; Humans; Male; Middle Aged; Posture; Vertigo
PubMed: 14517129
DOI: No ID Found -
Biomedicine & Pharmacotherapy =... Jan 2023Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis... (Review)
Review
Administration of cisplatin, a common chemotherapeutic drug, has an inevitable side effect of sensorineural hearing loss. The main etiologies are stria vascularis injury, spiral ganglion degeneration, and hair cell death. Over several decades, the research scope of cisplatin-induced ototoxicity has expanded with the discovery of the molecular mechanism mediating inner ear cell death, highlighting the roles of reactive oxygen species and transport channels for cisplatin uptake into inner ear cells. Upon entering hair cells, cisplatin disrupts organelle metabolism, induces oxidative stress, and targets DNA to cause intracellular damage. Recent studies have also reported the role of inflammation in cisplatin-induced ototoxicity. In this article, we preform a narrative review of the latest reported molecular mechanisms of cisplatin-induced ototoxicity, from extracellular to intracellular. We build up a signaling network starting with cisplatin entering into the inner ear through the blood labyrinth barrier, disrupting cochlear endolymph homeostasis, and activating inflammatory responses of the outer hair cells. After entering the hair cells, cisplatin causes hair cell death via DNA damage, redox system imbalance, and mitochondrial and endoplasmic reticulum dysfunction, culminating in programmed cell death including apoptosis, necroptosis, autophagic death, pyroptosis, and ferroptosis. Based on the mentioned mechanisms, prominent therapeutic targets, such as channel-blocking drugs of cisplatin transporter, construction of cisplatin structural analogues, anti-inflammatory drugs, antioxidants, cell death inhibitors, and others, were collated. Considering the recent research efforts, we have analyzed the feasibility of the aforementioned therapeutic strategies and proposed our otoprotective approaches to overcome cisplatin-induced ototoxicity.
Topics: Humans; Cisplatin; Antineoplastic Agents; Hair Cells, Auditory; Ototoxicity; Cochlea; Apoptosis
PubMed: 36455457
DOI: 10.1016/j.biopha.2022.114045 -
Environmental Research Dec 2023Meniere's disease (MD) is a severe inner ear condition known by debilitating symptoms, including spontaneous vertigo, fluctuating and progressive hearing loss, tinnitus,... (Review)
Review
Meniere's disease (MD) is a severe inner ear condition known by debilitating symptoms, including spontaneous vertigo, fluctuating and progressive hearing loss, tinnitus, and aural fullness or pressure within the affected ear. Prosper Meniere first described the origins of MD in the 1860s, but its underlying mechanisms remain largely elusive today. Nevertheless, researchers have identified a key histopathological feature called Endolymphatic Hydrops (ELH), which refers to the excessive buildup of endolymph fluid in the membranous labyrinth of the inner ear. The exact root of ELH is not fully understood. Still, it is believed to involve several biological and bioenvironmental etiological factors such as genetics, autoimmunity, infection, trauma, allergy, and new theories, such as saccular otoconia blocking the endolymphatic duct and sac. Regarding treatment, there are no reliable and definitive cures for MD. Most therapies focus on managing symptoms and improving the overall quality of patients' life. To make significant advancements in addressing MD, it is crucial to gain a fundamental understanding of the disease process, laying the groundwork for more effective therapeutic approaches. This paper provides a comprehensive review of the pathophysiology of MD with a focus on old and recent theories. Current treatment strategies and future translational approaches (with low-level evidence but promising results) related to MD are also discussed, including patents, drug delivery, and nanotechnology, that may provide future benefits to patients suffering from MD.
Topics: Humans; Meniere Disease; Endolymphatic Hydrops; Otolithic Membrane
PubMed: 37648189
DOI: 10.1016/j.envres.2023.116972 -
Physiological Research May 2018This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K(+) and Ca(2+) in... (Review)
Review
This review is focused on the unusual composition of the endolymph of the inner ear and its function in mechanoelectrical transduction. The role of K(+) and Ca(2+) in excitatory influx, the very low Na(+), Ca(2+) and Mg(2+) concentrations of endolymph, stereocilia structure of hair cells and some proteins involved in mechanosensory signal transduction with emphasis on auditory receptors are presented and analyzed in more details. An alternative hypothetical model of ciliary structure and endolymph with a 'normal' composition is discussed. It is concluded that the unique endolymph cation content is more than an energy saving mechanism that avoids disturbing circulatory vibrations to achieve a much better mechanosensory resolution. It is the only possible way to fulfil the requirements for a precise ciliary mechanoelectrical transduction in conditions where pressure events with quite diverse amplitudes and duration are transformed into adequate hair cell membrane depolarizations, which are regulated by a sensitive Ca(2+)-dependent feedback tuning.
Topics: Animals; Ear, Inner; Endolymph; Hair Cells, Auditory, Inner; Humans; Mechanotransduction, Cellular
PubMed: 29303598
DOI: 10.33549/physiolres.933684 -
Clinical and Experimental... Feb 2022Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of... (Review)
Review
Meniere disease (MD) is a rare set of conditions associated with the accumulation of endolymph in the cochlear duct and the vestibular labyrinth with a decrease of endocochlear potential. It is considered a chronic inflammatory disorder of the inner ear with a multifactorial origin. The clinical syndrome includes several groups of patients with a core phenotype: sensorineural hearing loss, episodes of vertigo, and tinnitus with a non-predictable course. Genetic factors and the innate immune response seem to play a central role in the pathophysiology of the condition. Autoimmune MD should be diagnosed if a patient fulfills the diagnostic criteria for MD and one of the following autoimmune disorders: autoimmune thyroid disease, psoriasis, autoimmune arthritis, ankylosing spondylitis, or systemic lupus erythematosus. We summarize the evidence to support autoimmune MD as an endophenotype in bilateral MD associated with the allelic variant rs4947296 and nuclear factor-kappa B (NF-κB)-mediated inflammation, the role of cytokines (particularly interleukin-1β and tumor necrosis factor-α) in defining a subset of patients with autoinflammation, and the potential role of cytokines as biomarkers to distinguish between patients with MD and vestibular migraine. Finally, we also introduce a list of potential drugs that could regulate the immune response in MD with potential for repurposing in clinical trials.
PubMed: 35124944
DOI: 10.21053/ceo.2021.00920