Round-window delivery of neurotrophin 3 regenerates cochlear synapses after acoustic overexposure.
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ABSTRACT:
SUBMITTER: Suzuki J
PROVIDER: S-EPMC4842978 | biostudies-other | 2016 Apr
REPOSITORIES: biostudies-other
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Project description:ObjectiveTo determine anatomic relationships and variation of the round window membrane to bony surgical landmarks on computed tomography.Study designRetrospective imaging review.Methods100 temporal bone images were evaluated. Direct measurements were obtained for membrane position. Vector distances and angulation from umbo and bony annulus were calculated from image viewer software coordinates.ResultsThe angle of round window membrane at junction with cochlear basal turn was (42.1 ± 8.6)°. The membrane's position relative to plane of the facial nerve through facial recess was (14.7 ± 5.2)° posterior from a reference line drawn through facial recess to carotid canal. Regarding transtympanic drug delivery, the round window membrane was directed 4.1 mm superiorly from the inferior annulus and 5.4 mm anteriorly from the posterior annulus. The round window membrane on average was angled superiorly from the inferior annulus (77.1 ± 27.9)° and slightly anteriorly from the posterior annulus (19.1 ± 11.1°). The mean distance of round window membrane from umbo was 4 mm and posteriorly rotated 30° clockwise from a perpendicular drawn from umbo to inferior annulus towards posterior annulus. Together, these measurements approximate the round window membrane in the tympanic membrane's posteroinferior quadrant.ConclusionsThese radiologic measurements demonstrate normal variations seen in round window anatomy relative to facial recess approach and bony tympanic annulus, providing a baseline to assess round window insertion for cochlear implantation and outlines anatomic factors affecting transtympanic drug delivery.
| S-EPMC7801246 | biostudies-literature
Project description:Background: The development of less traumatic surgical techniques, such as the round window approach (RWA), as well as the use of flexible electrodes and post-operative steroid administration have enabled the preservation of residual hearing after cochlear implantation (CI) surgery. However, consideration must still be given to the complications that can accompany CI. One such potential complication is the impairment of vestibular function with resulting vertigo symptoms. The aim of our current study was to examine the changes in vestibular function after implantation in patients who received CI using less traumatic surgery, particularly the RWA technique. Methods: Sixty-six patients who received CI in our center were examined by caloric testing, cervical vestibular evoked myogenic potential (cVEMP) and ocular VEMP (oVEMP) before or after implantation, or both, to obtain data on semicircular canal, saccular and utricular function, respectively. Less traumatic CI surgery was performed by the use of the RWA and insertion of flexible electrodes such as MED-EL FLEX soft, FLEX 28, and FLEX 24 (Innsbruck, Austria). Results: Caloric response and the asymmetry ratio of cVEMP and oVEMP were examined before and after implantation using less traumatic surgical techniques. Compared with before implantation, 93.9, 82.4, and 92.5% of the patients showed preserved vestibular function after implantation based on caloric testing, cVEMP and oVEMP results, respectively. We also examined the results for vestibular function by a comparison of the 66 patients using the RWA and flexible electrodes, and 17 patients who underwent cochleostomy and insertion of conventional or hard electrodes. We measured responses using caloric testing, cVEMP and oVEMP in patients after CI. There were no differences in the frequencies of abnormal caloric and oVEMP results in the implanted ears between the RWA and cochleostomy. On the other hand, the frequency of abnormal cVEMP responses in the implanted ears in the patients who received implantation by cochleostomy was significantly higher than that in the patients undergoing surgery using the RWA. Conclusion: Patients receiving CI using less traumatic surgical techniques such as RWA and flexible electrodes have reduced risk of damage to vestibular function.
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Project description:Cochlear gene therapy holds promise for the treatment of genetic deafness. Assessing its impact in adult murine models of hearing loss, however, has been hampered by technical challenges that have made it difficult to establish a robust method to deliver transgenes to the mature murine inner ear. Here in we demonstrate the feasibility of a combined round window membrane injection and semi-circular canal fenestration technique in the adult cochlea. Injection of both AAV2/9 and AAV2/Anc80L65 via this approach in P15-16 and P56-60 mice permits robust eGFP transduction of virtually all inner hair cells throughout the cochlea with variable transduction of vestibular hair cells. Auditory thresholds are not compromised. Transduction rate and cell tropism is primarily influenced by viral titer and AAV serotype but not age at injection. This approach is safe, versatile and efficient. Its use will facilitate studies using cochlear gene therapy in murine models of hearing loss over a wide range of time points.
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Project description:The feasibility of low frequency pure tone generation in the inner ear by laser-induced nonlinear optoacoustic effect at the round window was demonstrated in three human cadaveric temporal bones (TB) using an integral pulse density modulation (IPDM). Nanosecond laser pulses with a wavelength in the near-infrared (NIR) region were delivered to the round window niche by an optical fiber with two spherical lenses glued to the end and a viscous gel at the site of the laser focus. Using IPDM, acoustic tones with frequencies between 20 Hz and 1 kHz were generated in the inner ear. The sound pressures in scala tympani and vestibuli were recorded and the intracochlear pressure difference (ICPD) was used to calculate the equivalent sound pressure level (eq. dB SPL) as an equivalent for perceived loudness. The results demonstrate that the optoacoustic effect produced sound pressure levels ranging from 140 eq. dB SPL at low frequencies ≤ 200 Hz to 90 eq. dB SPL at 1 kHz. Therefore, the produced sound pressure level is potentially sufficient for patients requiring acoustic low frequency stimulation. Hence, the presented method offers a potentially viable solution in the future to provide the acoustic stimulus component in combined electro-acoustic stimulation with a cochlear implant.
| S-EPMC11001906 | biostudies-literature
Project description:Learning-induced trophic activity is thought to be critical for maintaining health of the aging brain. We report here that learning, acting through an unexpected pathway, activates synaptic receptors for one of the brain's primary trophic factors. Unsupervised learning, but not exploratory activity alone, robustly increased the number of postsynaptic densities associated with activated (phosphorylated) forms of BDNF's TrkB receptor in adult rat hippocampus; these increases were blocked by an NMDA receptor antagonist. Similarly, stimulation of hippocampal slices at the learning-related theta frequency increased synaptic TrkB phosphorylation in an NMDA receptor-dependent fashion. Theta burst stimulation, which was more effective in this regard than other stimulation patterns, preferentially engaged NMDA receptors that, in turn, activated Src kinases. Blocking the latter, or scavenging extracellular TrkB ligands, prevented theta-induced TrkB phosphorylation. Thus, synaptic TrkB activation was dependent upon both ligand presentation and postsynaptic signaling cascades. These results show that afferent activity patterns and cellular events involved in memory encoding initiate BDNF signaling through synaptic TrkB, thereby ensuring that learning will trigger neurotrophic support.
| S-EPMC2872439 | biostudies-literature
Project description:In mammalian hearing, type-I afferent auditory nerve fibers comprise the basis of the afferent auditory pathway. They are connected to inner hair cells of the cochlea via specialized ribbon synapses. Auditory nerve fibers of different physiological types differ subtly in their synaptic location and morphology. Low-spontaneous-rate auditory nerve fibers typically connect on the modiolar side of the inner hair cell, while high-spontaneous-rate fibers are typically found on the pillar side. In aging and noise-damaged ears, this fine-tuned balance between auditory nerve fiber populations can be disrupted and the functional consequences are currently unclear. Here, using immunofluorescent labeling of presynaptic ribbons and postsynaptic glutamate receptor patches, we investigated changes in synaptic morphology at three different tonotopic locations along the cochlea of aging gerbils compared to those of young adults. Quiet-aged gerbils showed about 20% loss of afferent ribbon synapses. While the loss was random at apical, low-frequency cochlear locations, at the basal, high-frequency location it almost exclusively affected the modiolar-located synapses. The subtle differences in volumes of pre- and postsynaptic elements located on the inner hair cell's modiolar versus pillar side were unaffected by age. This is consistent with known physiology and suggests a predominant, age-related loss in the low-spontaneous-rate auditory nerve population in the cochlear base, but not the apex.
| S-EPMC10931817 | biostudies-literature
Project description:OBJECTIVE:To establish whether the round window approach (RWA) leads to less vestibular dysfunction and dizziness than the standard cochleostomy approach (SCA) during cochlear implant (CI) surgery, as assessed using the video head impulse test (vHIT).Additionally, objective findings were compared with the subjective dizziness perceived by the patient. STUDY DESIGN:Double blinded, clinical randomized trial. SETTING:University Hospital. PATIENTS:Fifty-two ears from 46 patients were included. Inclusion criterion was a gain value more than 0.50. INTERVENTION:Patients were randomized to the RWA or the SCA. Evaluation with the vHIT was performed before surgery, 1 day after surgery, and 1 month after surgery. Subjective dizziness was measured using a visual analogue scale (VAS) and the dizziness handicap inventory (DHI). MAIN OUTCOME MEASURES:Gain values and the incidence of catch-up saccades. RESULTS:Three out of 23 patients in the SCA group experienced catch-up saccades compared with no patients in the RWA group, indicating the occurrence of objective vestibular dysfunction after CI surgery; the difference was not statistically significant. The VAS increased in both groups the day after surgery. The difference between the groups was not statistically significant. No statistically significant changes in the gain value or the DHI score could were observed between the two groups. CONCLUSION:No statistically significant difference between the cochleostomy approach and the round window approach using the vHIT and subjective dizziness perceived by the patient was found.
| S-EPMC5821484 | biostudies-literature
Project description:Recent work shows that acoustic overexposures causing only transient threshold elevation, and no hair cell loss, nevertheless can cause irreversible loss of the synapses between inner hair cells and cochlear nerve fibers (Kujawa and Liberman 2009). This cochlear synaptopathy, which is selective for the subset of sensory fibers with high thresholds and low spontaneous rates (Furman et al. 2013), appeared fully developed at 24-h post-exposure and showed no recovery by 8 weeks. However, prior studies of this synaptopathy counted only pre-synaptic ribbons, did not examine post-exposure times less than 24 h, and did not analyze the spatial patterns of degeneration around the hair cell circumference. Here, we immunostained for pre-synaptic ribbons, post-synaptic terminals and glutamate receptor patches, as well as the hair cell cytoplasm in noise-exposed and control mice to address the dynamics and spatial organization of the synaptopathic process as a function of post-exposure time from 0 h to 2 weeks. Our analysis showed that the loss of synaptic elements is nearly complete immediately after the 2-h exposure, that there is a reversible downregulation of gluR expression in the peripheral terminals which may be part of a protective mechanism, that there may be reversible reorganization of synaptic locations immediately after exposure, and that the spatial patterns are consistent with the idea that low-SR fibers are mainly found on the modiolar face of the hair cell and are the most vulnerable to noise-induced degeneration.
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Project description:Most implantable hearing aids currently available were developed to compensate the sensorineural hearing loss by driving middle ear structures (e.g., the ossicles). These devices are successfully used in round window (RW) stimulation clinically, although this was initially not the intended use. Here, a novel microactuator, specifically designed for RW stimulation, was tested in human temporal bones to determine actuator performance and applicability.Stapes footplate response to RW stimulation was determined experimentally in human temporal bones and the obtained sound pressure output level was estimated.The actuator had a flat displacement response between 0.125 and 4?kHz, a resonance between 4 and 7?kHz, and a roll-off above. At increasing contact force, the stapes footplate displacement decreased by 5-10?dB re ?m for forces ? 2?mN. The equivalent sound pressure level between 0.125 and 4?kHz amounted to 87-97?eq?dB SPL and increased to 117?eq?dB SPL for frequencies of 4-7?kHz. The total harmonic distortion (THD) of the actuator ranged within 15-40% for static forces of 5?mN.The feasibility of an electromagnetic actuator that may be placed into the RW niche was demonstrated but requires further optimization in terms of THD and static force sensitivity.
| S-EPMC5682051 | biostudies-literature
Project description:Objectives/hypothesisTo determine the timing of acoustic hearing changes among hearing preservation Cochlear implant (CI) recipients. To determine differences in hearing outcomes based on device type and demographic factors. To determine if there is a relationship between the extent of early hearing loss after CI and the subsequent rate of continued hearing loss.Study designProspective, single subject study.MethodsTwo hundred and eleven subjects who received a hearing preservation CI were included in the study-80 Nucleus Hybrid L24 (Cochlear), 47 422/522 (Cochlear), 24 S8 (Cochlear), 14 S12 (Cochlear), 6 SRW (Cochlear), 21 SLIM J (Advanced Bionics), and 19 Flex (Med-EL). Of these, 127 were included in the subsequent analyses. Audiometric thresholds (low frequency pure-tone-averages) were collected and compared pre and postoperatively.ResultsLong-term hearing preservation rates were 65% (52/80) for L24, 83% (20/24) for S8, 79% (11/14) for S12, 83% (5/6) for SRW, 54% (25/47) for 422/522, 91% (21/23) for SLIM J, and 84% (16/19) for Flex. Hearing loss was not related to device type (P = .9105) or gender (P = .2169). Older subjects (age ≥65) had worse hearing outcomes than younger subjects after initial device activation (age <65, P = .0262). There was no significant difference in rate of hearing loss over time between older and younger patients (P = .0938). Initial postoperative hearing loss was not associated with the rate of long-term hearing loss.ConclusionsLong-term low frequency hearing preservation is possible for CI recipients and is not associated with gender or device type. Rate of hearing loss over time is not dependent on patient age. Early hearing loss after CI does not predict the rate of long-term hearing loss.Level of evidence3 Laryngoscope, 132:2036-2043, 2022.
| S-EPMC9177890 | biostudies-literature