Search Results (10)

Noise-induced hearing loss (NIHL) is a significant occupational health issue, characterized by permanent damage to the cochlea due to prolonged exposure to high-intensity noise. Circulating microRNAs (c-miRNAs) have emerged as promising non-invasive indicators of inner ear pathology and potential modulators of cellular stress responses. Nevertheless, their specific roles in NIHL remain inadequately characterized. This study evaluated miRNA expression in the peripheral blood of individuals with bilateral NIHL (n = 12) and matched healthy controls (n = 6) using GeneChip^® miRNA 4.0 arrays. The Transcriptome Analysis Console software was used for differential expression analysis, and bioinformatic predictions of gene targets and pathway enrichment were performed using TargetScan (version 8.0) and the Enrichr tool. Among the 72 differentially expressed miRNAs (FDR < 0.05), hsa-miR-486-2, hsa-miR-664b-3p, hsa-miR-4485, hsa-miR-501, and hsa-miR-663b were notably upregulated, while hsa-miR-6723, hsa-miR-194-2, hsa-miR-668-5p, hsa-miR-4722-3p, and hsa-miR-4716 showed significant downregulation. Enrichment analyses indicated involvement in apoptosis regulation, mitochondrial stability, and cell cycle control. Principal component analysis (PCA) and clustering methods revealed clear molecular distinctions between the patient and control groups. The observed alterations in c-miRNA profiles highlight their relevance to NIHL-related cellular stress and degeneration. These findings support their utility as candidate biomarkers for diagnosis and prognosis, warranting further validation in functional and longitudinal studies. Full article

Introduction: Transimpedance matrix measurement (TIM) is an electrophysiological measurement protocol of the impedance patterns of electrode contacts within the cochlea. Several studies have reported that TIM is an effective tool for the identification of abnormal electrode array placement. However, the normative values for properly inserted electrodes, as well as correlation of the TIM patterns with the electrode position, are not completely determined. Objectives: The first aim of this study is to establish normative values of TIM measurements obtained in children with proper electrode array insertion and tip fold-over, with proper inner ear anatomy and in congenital anomalies. The second aim of this study is to compare TIM measurements in Slim Modiolar (SM) and in Contour Advance (CA) electrodes, as their position is different according to the modiolus proximity. Methods: A total of 55 pediatric patients were included in the study and underwent cochlear implantation. 62 intraoperative measurements were conducted in this group—50 in children with normal inner ear anatomy and 12 in children with inner ear malformations. After each implantation, a plain x-ray was obtained. Results: There were clear statistically significant differences in TIM patterns in patients where electrode fold-over was confirmed and between SM and CA electrodes. Conclusions: TIM is a promising technique for intraoperative analysis of electrode placement. TIM patterns differ and correlate consistently with the different models of array implanted. This study is the first to report TIM patterns observed in children with normal inner ear anatomy and in inner ear malformations. Full article

Multi-pitch perception is investigated in a listening test using 30 recordings of musical sounds with two tones played simultaneously, except for two gong sounds with inharmonic overtone spectra, judging roughness and separateness as the ability to tell the two tones in each recording apart. Of the sounds, 13 were from a Western guitar playing all 13 intervals in one octave, the other sounds were mainly from non-Western instruments, comparing familiar with unfamiliar instrument sounds for Western listeners. Additionally the sounds were processed in a cochlea model, transferring the mechanical basilar membrane motion into neural spikes followed by post-processing simulating different degrees of coincidence detection. Separateness perception showed a clear distinction between familiar and unfamiliar sounds, while roughness perception did not. By correlating perception with simulation different perception strategies were found. Familiar sounds correlated strongly positively with high degrees of coincidence detection, where only 3–5 periodicities were left, while unfamiliar sounds correlated with low coincidence levels. This corresponds to an attention to pitch and timbre, respectively. Additionally, separateness perception showed an opposite correlation between perception and neural correlates between familiar and unfamiliar sounds. This correlates with the perceptional finding of the distinction between familiar and unfamiliar sounds with separateness. Full article

Globally, over the next few decades, more than 2.5 billion people will suffer from hearing impairment, including profound hearing loss, and millions could potentially benefit from a cochlea implant. To date, several studies have focused on tissue trauma caused by cochlea implantation. The direct immune reaction in the inner ear after an implantation has not been well studied. Recently, therapeutic hypothermia has been found to positively influence the inflammatory reaction caused by electrode insertion trauma. The present study aimed to evaluate the hypothermic effect on the structure, numbers, function and reactivity of macrophages and microglial cells. Therefore, the distribution and activated forms of macrophages in the cochlea were evaluated in an electrode insertion trauma cochlea culture model in normothermic and mild hypothermic conditions. In 10-day-old mouse cochleae, artificial electrode insertion trauma was inflicted, and then they were cultured for 24 h at 37 °C and 32 °C. The influence of mild hypothermia on macrophages was evaluated using immunostaining of cryosections using antibodies against IBA1, F4/80, CD45 and CD163. A clear influence of mild hypothermia on the distribution of activated and non-activated forms of macrophages and monocytes in the inner ear was observed. Furthermore, these cells were located in the mesenchymal tissue in and around the cochlea, and the activated forms were found in and around the spiral ganglion tissue at 37 °C. Our findings suggest that mild hypothermic treatment has a beneficial effect on immune system activation after electrode insertion trauma. Full article

In this review, we discuss the role of liver X receptors (LXRs) in glial cells (microglia, oligodendrocytes and astrocytes) in the central nervous system (CNS). LXRs are oxysterol-activated nuclear receptors that, in adults, regulate genes involved in cholesterol homeostasis, the modulation of inflammatory responses and glutamate homeostasis. The study of LXR knockout mice has revealed that LXRβ plays a key role in maintaining the health of dopaminergic neurons in the substantia nigra, large motor neurons in the spinal cord and retinal ganglion cells in the eye. In the peripheral nervous system (PNS), LXRβ is responsible for the health of the spiral ganglion neurons (SGNs) in the cochlea. In addition, LXRs are essential for the homeostasis of the cerebrospinal fluid (CSF), and in LXRαβ^−/− mice, the lateral ventricles are empty and lined with lipid-laden cells. As LXRαβ^−/− mice age, lipid vacuoles accumulate in astrocytes surrounding blood vessels. By seven months of age, motor coordination becomes impaired, and there is a loss of motor neurons in the spinal cord of LXRβ^−/− mice. During development, migration of neurons in the cortex and cerebellum is retarded in LXRβ^−/− mice. Since LXRs are not expressed in dopaminergic or motor neurons in adult mice, the neuroprotective effects of LXRs appear to come from LXRs in glial cells where they are expressed. However, despite the numerous neurological deficits in LXR^−/− rodents, multiple sclerosis has the clear distinction of being the only human neurodegenerative disease in which defective LXR signaling has been identified. In this review, we summarize the regulation and functions of LXRs in glial cells and analyze how targeting LXRs in glial cells might, in the future, be used to treat neurodegenerative diseases and, perhaps, disorders caused by aberrant neuronal migration during development. Full article

Noise trauma-induced loss of ribbon synapses at the inner hair cells (IHC) of the cochlea may lead to hearing loss (HL), resulting in tinnitus. We are convinced that a successful and sustainable therapy of tinnitus has to treat both symptom and cause. One of these causes may be the mentioned loss of ribbon synapses at the IHC of the cochlea. In this study, we investigated the possible preventive and curative effects of the Ginkgo biloba extract EGb 761^® on noise-induced synaptopathy, HL, and tinnitus development in Mongolian gerbils (Meriones unguiculatus). To this end, 37 male animals received EGb 761^® or placebo orally 3 weeks before (16 animals) or after (21 animals) a monaural acoustic noise trauma (2 kHz, 115 dB SPL, 75 min). Animals’ hearing thresholds were determined by auditory brainstem response (ABR) audiometry. A possible tinnitus percept was assessed by the gap prepulse inhibition acoustic startle reflex (GPIAS) response paradigm. Synaptopathy was quantified by cochlear immunofluorescence histology, counting the ribbon synapses of 15 IHCs at 11 different cochlear frequency locations per ear. We found a clear preventive effect of EGb 761^® on ribbon synapse numbers with the surprising result of a significant increase in synaptic innervation on the trauma side relative to placebo-treated animals. Consequently, animals treated with EGb 761^® before noise trauma did not develop a significant HL and were also less affected by tinnitus compared to placebo-treated animals. On the other hand, we did not see a curative effect (EGb 761^® treatment after noise trauma) of the extract on ribbon synapse numbers and, consequently, a significant HL and no difference in tinnitus development compared to the placebo-treated animals. Taken together, EGb 761^® prevented noise-induced HL and tinnitus by protecting from noise trauma-induced cochlear ribbon synapse loss; however, in our model, it did not restore lost ribbon synapses. Full article

Objectives: (1) To analyze the preferential pathways of sound transmission and sound waves travelling properties in the skull and (2) to identify the location(s) on the skull where bone conduction to the cochlea is optimal. Study design: Basic research Methods: Nine cadaveric heads were placed in an anechoic chamber and equipped with six Bone Anchored Hearing Aids (BAHA™) implants (Cochlear™, Sydney, NSW, Australia) and fifteen accelerometers. A laser velocimeter was used to measure cochlear response by placing a reflector on the round window. Different frequency sweeps were applied to each implant, and measurements were recorded simultaneously by the laser velocimeter and accelerometers. Results: Low-frequency sound waves mostly travel the frontal transmission pathways, and there is no clear predominant pattern for the high frequencies. The mean inter-aural time lag is 0.1 ms. Optimal sound transmission to the cochlea occurs between 1000 and 2500 Hz with a contralateral 5 to 10 dB attenuation. The implant location does not influence mean transmission to the cochlea. Conclusion: There is a pattern of transmission for low frequencies through a frontal pathway but none for high frequencies. We were also able to demonstrate that the localization of the BAHA™ implant on the skull had no significant impact on the sound transmission, either ipsi or contralaterally. Full article

Cochlear implant is the method of choice for the rehabilitation of severe to profound sensorineural hearing loss. The study of the tissue response to cochlear implantation and the prevention of post-cochlear-implant damages are areas of interest in hearing protection research. The objective was to assess the efficacy of dexamethasone-eluting electrode array on endo canal fibrosis formation by three-dimensional immunofluorescence analysis in implanted Mongolian gerbil cochlea. Two trials were conducted after surgery using Mongolian gerbil implanted with dexamethasone-eluting or non-eluting intracochlear electrode arrays. The animals were then euthanised 10 weeks after implantation. The cochleae were prepared (electrode array in place) according to a 29-day protocol with immunofluorescent labelling and tissue clearing. The acquisition was carried out using light-sheet microscopy. Imaris software was then used for three-dimensional analysis of the cochleae and quantification of the fibrotic volume. The analysis of 12 cochleae showed a significantly different mean volume of fibrosis (2.16 × 10⁸ μm³ ± 0.15 in the dexamethasone eluting group versus 3.17 × 10⁸ μm³ ± 0.54 in the non-eluting group) (p = 0.004). The cochlear implant used as a corticosteroid delivery system appears to be an encouraging device for the protection of the inner ear against fibrosis induced by implantation. Three-dimensional analysis of the cochlea by light-sheet microscopy was suitable for studying post-implantation tissue damage. Full article

In recent years sensorineural hearing loss was found to affect not exclusively, nor at first, the sensory cells of the inner ear. The sensory cells’ synapses and subsequent neurites are initially damaged. Auditory synaptopathies also play an important role in cochlear implant (CI) care, as they can lead to a loss of physiological hearing in patients with residual hearing. These auditory synaptopathies and in general the cascades of hearing pathologies have been in the focus of research in recent years with the aim to develop more targeted and individually tailored therapeutics. In the current study, a method to examine implanted inner ears of guinea pigs was developed to examine the synapse level. For this purpose, the cochlea is made transparent and scanned with the implant in situ using confocal laser scanning microscopy. Three different preparation methods were compared to enable both an overview image of the cochlea for assessing the CI position and images of the synapses on the same specimen. The best results were achieved by dissection of the bony capsule of the cochlea. Full article

Central auditory processing disorder (CAPD) is associated with difficulties hearing and processing acoustic information, as well as subsequent impacts on the development of higher-order cognitive processes (i.e., attention and language). Yet CAPD also lacks clear and consistent diagnostic criteria, with widespread clinical disagreement on this matter. As such, identification of biological markers for CAPD would be useful. A recent genome association study identified a potential CAPD risk gene, USH2A. In a homozygous state, this gene is associated with Usher syndrome type 2 (USH2), a recessive disorder resulting in bilateral, high-frequency hearing loss due to atypical cochlear hair cell development. However, children with heterozygous USH2A mutations have also been found to show unexpected low-frequency hearing loss and reduced early vocabulary, contradicting assumptions that the heterozygous (carrier) state is “phenotype free”. Parallel evidence has confirmed that heterozygous Ush2a mutations in a transgenic mouse model also cause low-frequency hearing loss (Perrino et al., 2020). Importantly, these auditory processing anomalies were still evident after covariance for hearing loss, suggesting a CAPD profile. Since usherin anomalies occur in the peripheral cochlea and not central auditory structures, these findings point to upstream developmental feedback effects of peripheral sensory loss on high-level processing characteristic of CAPD. In this study, we aimed to expand upon the mouse behavioral battery used in Perrino et al. (2020) by evaluating central auditory brain structures, including the superior olivary complex (SOC) and medial geniculate nucleus (MGN), in heterozygous and homozygous Ush2a mice. We found that heterozygous Ush2a mice had significantly larger SOC volumes while homozygous Ush2a had significantly smaller SOC volumes. Heterozygous mutations did not affect the MGN; however, homozygous Ush2a mutations resulted in a significant shift towards more smaller neurons. These findings suggest that alterations in cochlear development due to USH2A variation can secondarily impact the development of brain regions important for auditory processing ability. Full article