In Vivo Cochlear imaging provides a tool to study endolymphatic hydrops

2020 ◽  
pp. 1-8
Author(s):  
Ido Badash ◽  
Brian E. Applegate ◽  
John S. Oghalai
Keyword(s):  
Hearing Loss ◽  
Endolymphatic Hydrops ◽  
Acoustic Trauma ◽  
Glutamate Excitotoxicity ◽  
Human Hearing ◽  
Blast Trauma ◽  
Improvised Explosive ◽  
Explosive Devices ◽  
Near Future

Exposure to noise trauma, such as that from improvised explosive devices, can lead to sensorineural hearing loss and a reduced quality of life. In order to elucidate the mechanisms underlying noise-induced hearing loss, we have adapted optical coherence tomography (OCT) for real-time cochlear visualization in live mice after blast exposure. We demonstrated that endolymphatic hydrops develops following blast injury, and that this phenomenon may be associated with glutamate excitotoxicity and cochlear synaptopathy. Additionally, osmotic stabilization of endolymphatic hydrops partially rescues cochlear synapses after blast trauma. OCT is thus a valuable research tool for investigating the mechanisms underlying acoustic trauma and dynamic changes in endolymph volume. It may also help with the diagnosis and treatment of human hearing loss and/or vertigo in the near future.

scholarly journals Osmotic stabilization prevents cochlear synaptopathy after blast trauma

2018 ◽  
Vol 115 (21) ◽  
pp. E4853-E4860 ◽  
Author(s):  
Jinkyung Kim ◽  
Anping Xia ◽  
Nicolas Grillet ◽  
Brian E. Applegate ◽  
John S. Oghalai
Keyword(s):  
Hearing Loss ◽  
Hair Cell ◽  
Hair Cells ◽  
Noise Exposure ◽  
Endolymphatic Hydrops ◽  
Surrogate Marker ◽  
Cell Loss ◽  
Hair Cell Loss ◽  
Blast Trauma

Traumatic noise causes hearing loss by damaging sensory hair cells and their auditory synapses. There are no treatments. Here, we investigated mice exposed to a blast wave approximating a roadside bomb. In vivo cochlear imaging revealed an increase in the volume of endolymph, the fluid within scala media, termed endolymphatic hydrops. Endolymphatic hydrops, hair cell loss, and cochlear synaptopathy were initiated by trauma to the mechanosensitive hair cell stereocilia and were K+-dependent. Increasing the osmolality of the adjacent perilymph treated endolymphatic hydrops and prevented synaptopathy, but did not prevent hair cell loss. Conversely, inducing endolymphatic hydrops in control mice by lowering perilymph osmolality caused cochlear synaptopathy that was glutamate-dependent, but did not cause hair cell loss. Thus, endolymphatic hydrops is a surrogate marker for synaptic bouton swelling after hair cells release excitotoxic levels of glutamate. Because osmotic stabilization prevents neural damage, it is a potential treatment to reduce hearing loss after noise exposure.

Development of Finite Element Rat Head Model to Study the Effect of Incident Pressure and Skull Rigidity Under Blast-Induced Biomechanical Loading

2013 ◽  
Author(s):  
A. Sundaramurthy ◽  
N. Chandra
Keyword(s):  
Finite Element ◽  
Element Model ◽  
Blast Waves ◽  
Head Model ◽  
Improvised Explosive Devices ◽  
Biomechanical Loading ◽  
In Vivo Animal Models ◽  
Improvised Explosive ◽  
Explosive Devices

Blast waves generated by improvised explosive devices (IEDs) cause traumatic brain injury (TBI) in soldiers and civilians. Currently, in vivo animal models are extensively used to study blast TBI, to identify mechanisms of injury, and to develop injury thresholds. This work focuses on the study of the effect of Incident Pressure (IP), skull rigidity on the measured Intracranial Pressure (ICP) and maximum principle strain measured on the skull using a validated finite element model of the rat head. Our results indicate that the ICP has a negative correlation with the skull rigidity; i.e., with increase in the skull rigidity the ICP tends to decrease. Similarly, ICP linearly increases with an increase in the IP. Finally, the strain has a negative non linear relationship with the skull rigidity.

scholarly journals Endolymphatic Hydrops in Fluctuating Hearing Loss and Recurrent Vertigo

2021 ◽  
Vol 8 ◽  
Author(s):  
Pablo Domínguez ◽  
Raquel Manrique-Huarte ◽  
Víctor Suárez-Vega ◽  
Nieves López-Laguna ◽  
Carlos Guajardo ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Odds Ratio ◽  
Endolymphatic Hydrops ◽  
Sensorineural Hearing ◽  
Vestibular Tests ◽  
Risk Of Progression ◽  
Magnetic Resonance Imaging Mri ◽  
Adjusted Model

Background: Endolymphatic hydrops (EH) is the histopathological hallmark of Ménière's disease (MD) and has been found by in vivo magnetic resonance imaging (MRI) in patients with several inner ear syndromes without definite MD criteria. The incidence and relevance of this finding is under debate.Purpose: The purpose of the study is to evaluate the prevalence and characteristics of EH and audiovestibular test results in groups of patients with fluctuating audiovestibular symptoms not fulfilling the actual criteria for definite MD and compare them with a similar group of patients with definite MD and a group of patients with recent idiopathic sudden neurosensory hearing loss (ISSNHL).Material and Methods: 170 patients were included, 83 with definite MD, 38 with fluctuating sensorineural hearing loss, 34 with recurrent vertigo, and 15 with ISSNHL. The clinical variables, audiovestibular tests, and EH were evaluated and compared. Logistic proportional hazard models were used to obtain the odds ratio for hydrops development, including a multivariable adjusted model for potential confounders.Results: No statistical differences between groups were found regarding disease duration, episodes, Tumarkin spells, migraine, vascular risk factors, or vestibular tests; only hearing loss showed differences. Regarding EH, we found significant differences between groups, with odds ratio (OR) for EH presence in definite MD group vs. all other patients of 11.43 (4.5–29.02; p < 0.001). If the ISSNHL group was used as reference, OR was 55.2 (11.9–253.9; p < 0.001) for the definite MD group, 9.9 (2.1–38.9; p = 0.003) for the recurrent vertigo group, and 5.1 (1.2–21.7; p = 0.03) for the group with fluctuating sensorineural hearing loss.Conclusion: The percentage of patients with EH varies between groups. It is minimal in the ISSNHL group and increases in groups with increasing fluctuating audiovestibular symptoms, with a rate of severe EH similar to the known rate of progression to definite MD in those groups, suggesting that presence of EH by MRI could be related to the risk of progression to definite MD. Thus, EH imaging in these patients is recommended.

Imaging of endolymphatic hydrops: A comprehensive update in primary and secondary hydropic ear disease

2021 ◽  
pp. 1-8
Author(s):  
Michael Eliezer ◽  
Arnaud Attyé ◽  
Michel Toupet ◽  
Charlotte Hautefort
Keyword(s):  
Hearing Loss ◽  
Sensorineural Hearing Loss ◽  
Inner Ear ◽  
Endolymphatic Hydrops ◽  
Meniere’S Disease ◽  
Sensorineural Hearing ◽  
Ménière’S Disease ◽  
Clinical Settings ◽  
Technical Developments

BACKGROUND: Since the first description by Hallpike and Cairns, the excess of endolymphatic fluid, also known as endolymphatic hydrops (EH), has been established as being the main biomarker in patients with Menière’s disease. Recently, the concept of primary (PHED) and secondary hydropic ear disease (SHED) has been introduced. PHED corresponded to Menière’s disease while SHED was defined as the presence of EH in patients with pre-existing inner ear disease. OBJECTIVE: In this article, we would like to summarize the methodology of hydrops exploration using MRI and the previously published radiological findings in patients with PHED and SHED. RESULTS: Before the emergence of delayed inner ear MRI, the presence of EH was assumed based on clinical symptoms. However, because of the recent technical developments, inner ear MRI became an important tool in clinical settings for identifying EH in vivo, in patients with PHED and SHED. The presence of EH on MRI is related with the degree of sensorineural hearing loss whether in patients with PHED or SHED. By contrast, in PHED or SHED patients without sensorineural hearing loss, MRI showed no sign of EH. CONCLUSIONS: Thanks to the recent technical developments, inner ear MRI became an important tool in clinical settings for identifying EH in vivo, in patients with PHED and SHED.

scholarly journals Myosin-driven Nucleation of Actin Filaments Drives Stereocilia Development Critical for Hearing

2021 ◽  
Author(s):  
Zane G Moreland ◽  
Fangfang Jiang ◽  
Carlos Aguilar ◽  
Melanie Barzik ◽  
Rui Gong ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Actin Polymerization ◽  
In Vitro Assays ◽  
Progressive Hearing Loss ◽  
Single Filament ◽  
Additional Function ◽  
Actin Regulatory Proteins ◽  
Human Hearing

The assembly and maintenance of actin-based mechanosensitive stereocilia in the cochlea is critical for lifelong hearing. Myosin-15 (MYO15) is hypothesized to modulate stereocilia height by trafficking actin regulatory proteins to their tip compartments, where actin polymerization must be precisely controlled during development. We identified a mutation (p.D1647G) in the MYO15 motor-domain that initially maintained trafficking, but caused progressive hearing loss by stunting stereocilia growth, revealing an additional function for MYO15. Consistent with its maintenance of tip trafficking in vivo, purified p.D1647G MYO15 modestly reduced actin-stimulated ATPase activity in vitro. Using ensemble and single-filament fluorescence in vitro assays, we demonstrated that wild-type MYO15 directly accelerated actin filament polymerization by driving nucleation, whilst p.D1647G MYO15 blocked this activity. Collectively, our studies suggest direct actin nucleation by MYO15 at the stereocilia tip is necessary for elongation in vivo, and that this is a primary mechanism disrupted in DFNB3 hereditary human hearing loss.

scholarly journals In Vivo Production of RNA Aptamers and Nanoparticles: Problems and Prospects

Molecules ◽  
2021 ◽  
Vol 26 (5) ◽  
pp. 1422
Author(s):  
Ousama Al Shanaa ◽  
Andrey Rumyantsev ◽  
Elena Sambuk ◽  
Marina Padkina
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Large Scale ◽  
Potential Model ◽  
Model Organism ◽  
Rna Aptamers ◽  
Early Stages ◽  
Near Future

RNA aptamers are becoming increasingly attractive due to their superior properties. This review discusses the early stages of aptamer research, the main developments in this area, and the latest technologies being developed. The review also highlights the advantages of RNA aptamers in comparison to antibodies, considering the great potential of RNA aptamers and their applications in the near future. In addition, it is shown how RNA aptamers can form endless 3-D structures, giving rise to various structural and functional possibilities. Special attention is paid to the Mango, Spinach and Broccoli fluorescent RNA aptamers, and the advantages of split RNA aptamers are discussed. The review focuses on the importance of creating a platform for the synthesis of RNA nanoparticles in vivo and examines yeast, namely Saccharomyces cerevisiae, as a potential model organism for the production of RNA nanoparticles on a large scale.

scholarly journals Regulator of G protein signaling 17 represents a novel target for treating cisplatin induced hearing loss

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Asmita Dhukhwa ◽  
Raheem F. H. Al Aameri ◽  
Sandeep Sheth ◽  
Debashree Mukherjea ◽  
Leonard Rybak ◽  
...  
Keyword(s):  
Hearing Loss ◽  
G Protein ◽  
Protein Interactions ◽  
Cannabinoid Receptor ◽  
Significant Proportion ◽  
G Protein Signaling ◽  
Protein Signaling ◽  
Drug Induced ◽  
Male Wistar Rats

AbstractRegulators of G protein signaling (RGS) accelerate the GTPase activity of G proteins to enable rapid termination of the signals triggered by G protein-coupled receptors (GPCRs). Activation of several GPCRs, including cannabinoid receptor 2 (CB2R) and adenosine A1 receptor (A1AR), protects against noise and drug-induced ototoxicity. One such drug, cisplatin, an anticancer agent used to treat various solid tumors, produces permanent hearing loss in experimental animals and in a high percentage of cancer patients who undergo treatments. In this study we show that cisplatin induces the expression of the RGS17 gene and increases the levels of RGS17 protein which contributes to a significant proportion of the hearing loss. Knockdown of RGS17 suppressed cisplatin-induced hearing loss in male Wistar rats, while overexpression of RGS17 alone produced hearing loss in vivo. Furthermore, RGS17 and CB2R negatively regulate the expression of each other. These data suggest that RGS17 mediates cisplatin ototoxicity by uncoupling cytoprotective GPCRs from their normal G protein interactions, thereby mitigating the otoprotective contributions of endogenous ligands of these receptors. Thus, RGS17 represents a novel mediator of cisplatin ototoxicity and a potential therapeutic target for treating hearing loss.

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