scholarly journals Uncoiling the Human Cochlea—Physical Scala Tympani Models to Study Pharmacokinetics Inside the Inner Ear

Life ◽  
2021 ◽  
Vol 11 (5) ◽  
pp. 373
Author(s):  
Daniel Schurzig ◽  
Max Fröhlich ◽  
Stefan Raggl ◽  
Verena Scheper ◽  
Thomas Lenarz ◽  
...  

In the field of cochlear implantation, artificial/physical models of the inner ear are often employed to investigate certain phenomena like the forces occurring during implant insertions. Up to now, no such models are available for the analysis of diffusion processes inside the cochlea although drug delivery is playing an increasingly important role in this field. For easy access of the cochlea along its whole profile, e.g., for sequential sampling in an experimental setting, such a model should ideally be longitudinal/uncoiled. Within this study, a set of 15 micro-CT imaging datasets of human cochleae was used to derive an average representation of the scala tympani. The spiral profile of this model was then uncoiled along different trajectories, showing that these trajectories influence both length and volume of the resulting longitudinal model. A volumetric analysis of the average spiral model was conducted to derive volume-to-length interrelations for the different trajectories, which were then used to generate two tubular, longitudinal scala tympani models with volume and length properties matching the original, spiral profile. These models can be downloaded for free and used for reproducible and comparable simulative and experimental investigations of diffusion processes within the inner ear.

1987 ◽  
Vol 253 (1) ◽  
pp. F50-F58 ◽  
Author(s):  
O. Sterkers ◽  
E. Ferrary ◽  
G. Saumon ◽  
C. Amiel

Kinetics of hydrophilic solute entry into endolymph (EL), perilymph (PL), and cerebrospinal fluid (CSF) were studied after intravenous administration (sodium, urea, glycerol, mannitol, sucrose) and cerebral lateral ventricle injection (urea, sucrose) of tracers in anesthetized rats. Samples of cochlear EL, PL of scala vestibuli (PLV), PL of scala tympani (PLT), and cisternal CSF were obtained. The data showed slow entry of tracers in PLV, PLT, and CSF as follows: Na greater than urea greater than mannitol approximately sucrose; slower entry of mannitol and sucrose in PLT and CSF than in PLV; 1 h delayed peak of radioactivity in PLV compared with the immediate peaks in PLT and CSF after CSF injection, and the value of PLV peak was 13% that in CSF; extremely slow entry of nonelectrolytes in EL. These results indicate that PLV originates mainly from plasma across a blood-perilymph barrier that restricts the entry of small hydrophilic solutes. The blood-perilymph barrier is most likely composed of an endothelial barrier associated with an epithelial secretion. The latter could be located at the vasculo-epithelial zone of the spiral limbus.


2012 ◽  
Vol 18 (2) ◽  
pp. 277-289 ◽  
Author(s):  
Roman M. Pavlovsky ◽  
Igor M. Lebedich ◽  
Michail Samofalov ◽  
Valerij V. Orliansky

The article discusses experimental investigations of wind effects and use of design codes for solving aerodynamic problems. It provides data regarding wind-tunnel tests conducted on three buildings with poorly streamlined shapes, including: methodology and test conditions, aerodynamic properties of the designed structures, features of physical models and research results. All three civil buildings are multi-purpose stadiums of the European level. Despite the identical functional purpose, each building has a unique shape and volume. The paper analyses and compares testing conditions in the wind tunnel and some selective results. The authors propose a criterion for estimating aerodynamic properties of the overhanging roof over spectator stands. The article also considers dependencies of model surface pressures on airflow directions under various test conditions. Santrauka Darbe trumpai apžvelgti vėjo poveikių eksperimentiniai tyrimai ir projektavimo normų taikymas aerodinamikos uždaviniams spręsti. Pateikti duomenys apie trijų sudėtingo pavidalo statinių maketų eksperimentinius tyrimus aero-dinaminiame vamzdyje: metodika ir bandymų sąlygos, projektuojamų statinių aerodinaminės savybės, ypatingi maketų bruožai, bandymų rezultatai. Visi trys statiniai – europinio lygio universalieji stadionai. Nepaisant bendrosios funkcinės paskirties, kiekvieno statinio pavidalas ir tūrinis sprendinys yra originalūs. Darbe gretinamos bandymų sąlygos ir pasirinktiniai rezultatai, pasiūlytas sportinių ir pramoginių statinių gembinio stogo virš žiūrovų tribųnų aerodinaminių savybių nagrinejimo kriterijus. Išanalizuotos slėgio ant maketų paviršių priklausomybės nuo oro srauto krypties, esant įvairiems bandymų variantams.


2014 ◽  
Vol 2014 ◽  
pp. 1-10 ◽  
Author(s):  
Chang-qiang Tan ◽  
Xia Gao ◽  
Lang Guo ◽  
He Huang

Bone marrow mesenchymal stem cells (BMSCs) expressing recombinant IL-4 have the potential to remediate inflammatory diseases. We thus investigated whether BMSCs expressing exogenous IL-4 could alleviate autoimmune sensorineural hearing loss. BMSCs isolated from guinea pigs were transfected with recombinant lentivirus expressing IL-4. A total of 33 animals were divided into three groups. Group A received scala tympani injection of IL-4-expressing BMSCs, and Group B received control vector-expressing BMSCs, and Group C received phosphate-buffered saline. The distribution of implanted BMSCs in the inner ears was assessed by immunohistochemistry and fluorescence microscopy. Auditory brain-stem response (ABR) was monitored to evaluate the auditory changes. Following BMSCs transplantation, the threshold levels of ABR wave III decreased in Groups A and B and significant differences were observed between these two groupsP<0.05. Transplanted BMSCs distributed in the scala tympani and scala vestibuli. In some ears with hearing loss, there was a decrease in the number of spiral ganglion cells and varying degrees of endolymphatic hydrops or floccule. Following transplantation, the lentivirus-infected BMSCs migrated to the inner ear and produced IL-4. Our results demonstrate that, upon transplantation, BMSCs and BMSCs expressing recombinant IL-4 have the ability to remediate the inflammatory injury in autoimmune inner ear diseases.


1991 ◽  
Vol 105 (8) ◽  
pp. 621-624 ◽  
Author(s):  
Christopher deSouza ◽  
Michael M. Paparella ◽  
Pat Schachern ◽  
Tae H. Yoon

AbstractOssification of the inner ear is the result of multifactorial pathogeneses, such as infection or malignant infiltration, and otosclerosis. Ossification of the innerear spaces is a well documented sequela of suppurative labyrinthitis. In this study of human temporal bones, sections from 14 patients (28 temporal bones)were studied. In additionto the osseous tissue within the inner ear, findings included neoplasms, otosclerosis, otitis media, trauma, and Fabry's disease. We have attempted to correlate these conditions and their influence on the formation of osseous tissue within the spaces of the inner ear. Tympanogenic infection and vascular compromise were found to play an important role in ossification. The scala tympani ofthe basal turn of the cochlea was frequently the site involved.


1997 ◽  
Vol 106 (12) ◽  
pp. 1070-1075 ◽  
Author(s):  
Tsuyoshi Takasu ◽  
Jeffrey P. Harris

The in vivo effect of systemic administration of monoclonal antibody (mAb) against ICAM-1 (αICAM-1) in experimental immune-mediated labyrinthitis was evaluated. The αICAM-1–treated rats showed reduced inflammatory cell infiltration in the scala tympani and the perisaccular tissue of the endolymphatic sac. However, with this experimental paradigm, labyrinthitis could not be completely abolished. These findings suggest that ICAM-1–dependent pathways play an important role in the series of immunologic events occurring in the inner ear, and that the use of ICAM-1 antagonist may be a possible therapeutic approach to labyrinthitis.


2010 ◽  
Vol 76 ◽  
pp. 16-24 ◽  
Author(s):  
Dieter Hofmann ◽  
Maria Entrialgo ◽  
Jürgen Reiche ◽  
Karl Kratz ◽  
Andreas Lendlein

Biodegradable polymers are applied in temporary implants, such as surgical sutures and controlled drug delivery systems. They are also of relevance in biomaterial-based Regenerative Therapies, where they provide a temporary substitute of the extra-cellular matrix. A major limitation of established degradable implant materials is the fact, that their degradation behavior can not be reliably predicted applying existing experimental methodologies. Therefore a knowledge-based approach is clearly needed to overcome this problem and to enable the tailored design of biodegradable polymers. Here we describe two methods, which can be applied in this approach: molecular modeling combining atomistic bulk and interface models with quantum chemical studies and experimental investigations of macromolecule degradation in Langmuir monolayers. The polymers utilized to exemplarily illustrate the concepts are aliphatic (co)polyesters [e.g. poly(-caprolactone) (PCL), polyglycolide (PGA), poly(rac-lactide) (PDLLA), poly[(rac-lactide)-co-glycolide] (PLGA)] and copoly(ether)esteruretanes as multiblock copolymers. The molecular modeling approach permits to efficiently investigate the influence of micro-structural properties like free volume distribution, cohesive energy density and concentration of polar functional groups on the bulk water uptake as one constituent part of hydrolytic degradation. The Langmuir monolayer investigations on polymer degradation on the other hand yield the dynamics of bond splitting during degradation within hours separately from time consuming diffusion processes, which may take months in bulk samples.


2015 ◽  
Vol 1 (1) ◽  
pp. 515-518 ◽  
Author(s):  
Thomas S. Rau ◽  
Josephine Granna ◽  
Thomas Lenarz ◽  
Omid Majdani ◽  
Jessica Burgner-Kahrs

AbstractThe aim of this study was to investigate the applicability of tubular manipulators as an actuator mechanism for intracochlear positioning of the electrode array (EA) of a cochlear implant (CI). This is motivated by the vision of an atraumatic insertion of the EA into the inner ear (cochlea) without any damage to the intracochlear structures in combination with a well-defined final position. To realize this, an actuator mechanism is required which allows consideration of the patient-specific anatomy. We propose a tubular manipulator for this task. It consists of three concentric tubes: A straight outer tube serves as a guiding sleeve to enter the inner ear (cochlea) and two additional telescoping, superelastic, helically precurved tubes. By selecting helical tube parameters of both tubes prior insertion, a patient-specific curling behaviour of the tubular manipulator can be achieved. For preliminary investigation, segmentation and skeletonization of 5 human scala tympani were performed to determine their centrelines. These centrelines were considered as individual ideal insertion paths. An optimization algorithm was developed to identify suitable tube set parameters (curvature, diameter, length, torsion, stiffness) as well as configuration parameters (translation and rotation of the 2 inner tubes). Different error values describing the deviation of the shape of the tubes with respect to the insertion path were used to quantify the optimization results. In all cases tube set parameters for a final position within the cochlea were found, while keeping the maximum error below 1mm. These preliminary results are promising in terms of the potential applicability of tubular manipulators for positioning auditory prosthesis inside the scala tympani of the inner ear.


2006 ◽  
Vol 129 (3) ◽  
pp. 279-292 ◽  
Author(s):  
Olivier Coutier-Delgosha ◽  
François Deniset ◽  
Jacques André Astolfi ◽  
Jean-Baptiste Leroux

This paper presents comparisons between two-dimensional (2D) CFD simulations and experimental investigations of the cavitating flow around a symmetrical 2D hydrofoil. This configuration was proposed as a test case in the “Workshop on physical models and CFD tools for computation of cavitating flows” at the 5th International Symposium on cavitation, which was held in Osaka in November 2003. The calculations were carried out in the ENSTA laboratory (Palaiseau, France), and the experimental visualizations and measurements were performed in the IRENav cavitation tunnel (Brest, France). The calculations are based on a single-fluid approach of the cavitating flow: the liquid/vapor mixture is treated as a homogeneous fluid whose density is controlled by a barotropic state law. Results presented in the paper focus on cavitation inception, the shape and the general behavior of the sheet cavity, lift and drag forces without and with cavitation, wall pressure signals around the foil, and the frequency of the oscillations in the case of unsteady sheet cavitation. The ability of the numerical model to predict successively the noncavitating flow field, nearly steady sheet cavitation, unsteady cloud cavitation, and finally nearly supercavitating flow is discussed. It is shown that the unsteady features of the flow are correctly predicted by the model, while some subtle arrangements of the two-phase flow during the condensation process are not reproduced. A comparison between the peer numerical results obtained by several authors in the same flow configuration is also performed. Not only the cavitation model and the turbulence model, but also the numerical treatment of the equations, are found to have a strong influence on the results.


1996 ◽  
Vol 110 (1) ◽  
pp. 13-18 ◽  
Author(s):  
Robert B. Ashman ◽  
John M. Papadimitriou ◽  
Alma Fulurija

AbstractThe yeastCandida albicansis an important opportunistic pathogen that has been associated with disease of the inner ear. This study describes the histopathology of acute labyrinthitis caused by systemic infection with C.albicansin ageing inbred mice. Within four days after infection, yeast and hyphal forms of C.albicanswere found in the membranous labyrinth. The utricle and the adjacent parts of the ampullary regions of the semicircular canals were most severely affected, but damage was also seen in the scala media, the Scala tympani, the saccule, and the scala vestibuli. In the utricle, the lining epithelium of the membranous labyrinth was disrupted, and the lining cells of the vestibular membrane showed foci in which the membrane was disrupted. The data suggest that age may represent a risk factor for fungal labyrinthitis.


Author(s):  
Eric Lehner ◽  
Matthias Menzel ◽  
Daniel Gündel ◽  
Stefan K. Plontke ◽  
Karsten Mäder ◽  
...  

AbstractThe effective delivery of drugs to the inner ear is still an unmet medical need. Local controlled drug delivery to this sensory organ is challenging due to its location in the petrous bone, small volume, tight barriers, and high vulnerability. Local intracochlear delivery of drugs would overcome the limitations of intratympanic (extracochlear) and systemic drug application. The requirements for such a delivery system include small size, appropriate flexibility, and biodegradability. We have developed biodegradable PLGA-based implants for controlled intracochlear drug release that can also be used in combination with cochlear implants (CIs), which are implantable neurosensory prosthesis for hearing rehabilitation. The drug carrier system was tested for implantation in the human inner ear in 11 human temporal bones. In five of the temporal bones, CI arrays from different manufacturers were implanted before insertion of the biodegradable PLGA implants. The drug carrier system and CI arrays were implanted into the scala tympani through the round window. Implanted temporal bones were evaluated by ultra-high-resolution computed tomography (µ-CT) to illustrate the position of implanted electrode carriers and the drug carrier system. The µ-CT measurements revealed the feasibility of implanting the PLGA implants into the scala tympani of the human inner ear and co-administration of the biodegradable PLGA implant with a CI array. Graphical abstract


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