Transcriptomic differences in cochlear cells isolated from mice implanted with dexamethason-eluting electrode arrays or standard electrode arrays
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PROVIDER: PRJNA1188990 | ENA |
REPOSITORIES: ENA
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Project description:The inflammatory foreign body response (FBR) following cochlear implantation (CI) can negatively impact CI outcomes, including increased electrode impedances. This study aims to investigate the long-term efficacy of dexamethasone eluting cochlear implant and locally delivered dexamethasone, a potent anti-inflammatory glucocorticoid, on the intracochlear FBR and electrical impedance post-implantation in a murine model. The left ears of CX3CR1+/GFP Thy1+/YFP (macrophage-neuron dual reporter) mice were implanted with dexamethasone-eluting cochlear implants (Dex-CI) or standard implant (Standard-CI) while the right ear served as unoperated control. Another group of dual reporter mice was implanted with a standard CI electrode array followed by injection of dexamethasone in the middle ear to mimic current clinical practice (Dex-local). Mouse implants were electrically stimulated with serial measurement of electrical impedance. Dex-CI reduced electrical impedance and inflammatory FBR in the murine model for an extended period. Dex-local in the murine model is ineffective for long-term reduction of FBR and electrode impedance. Our data suggest that dexamethasone eluting arrays are more effective than the current clinical practice of locally applied dexamethasone in reducing FBR and electrical impedance.
2025-07-17 | GSE282478 | GEO
Project description:Spatiotemporal Patterns of Gene Expression Around Implanted Silicon Electrode Arrays
| PRJNA1070633 | ENA
Project description:Objective. Intracortical brain interfaces are an ever evolving technology with growing potential for clinical and research applications. The chronic tissue response to these devices traditionally has been characterized by glial scarring, inflammation, oxidative stress, neuronal loss, and blood-brain barrier disruptions. The full complexity of the tissue response to implanted devices is still under investigation. Approach. In this study, we have utilized RNA-sequencing to identify the spatiotemporal gene expression patterns in interfacial (within 100 µm) and distal (500 µm from implant) brain tissue around implanted silicon microelectrode arrays. Naïve, unimplanted tissue served as a control. Main results. The data revealed significant overall differential expression (DE) in contrasts comparing interfacial tissue vs naïve (157 DE genes), interfacial vs distal (94 DE genes), and distal vs naïve tissues (21 DE genes). Our results captured previously characterized mechanisms of the foreign body response, such as astroglial encapsulation, as well as novel mechanisms which have not yet been characterized in the context of indwelling neurotechnologies. In particular, we have observed perturbations in multiple neuron-associated genes which potentially impact the intrinsic function and structure of neurons at the device interface. In addition to neuron-associated genes, the results presented in this study identified significant DE in genes which are associated with oligodendrocyte, microglia, and astrocyte involvement in the chronic tissue response. Significance. The results of this study increase the fundamental understanding of the complexity of tissue response in the brain and provide an expanded toolkit for future investigation into the bio-integration of implanted electronics with tissues in the central nervous system.
2024-02-05 | GSE254474 | GEO
Project description:To investigate the effect of the dexamethasone-eluting electrode in the guinea pig cochlea, and compared the gene expression after 7 days insertion with that of a normal electrode or non-treated control by microarray. Male Hartley guinea pigs (SLC, Shizuoka, Japan) with an age of seven weeks were used for the study. Three were implanted with normal electrodes while three others received a dexamethasone-eluting electrode. The cochleae from two animals, which did not undergo surgery. Seven days after electrode implantation the whole temporal bone was removed and placed into RNAlater solution (Ambion, Life Technologies Co., Grand Island, NY) to stabilize and protect cellular RNA. The whole cochlea was dissected out under a microscope and total RNA were extracted.
2014-01-17 | E-GEOD-53866 | biostudies-arrayexpress
Project description:HypothesisCochlear duct length (CDL) can be automatically measured for custom selection of cochlear implant (CI) electrode arrays.BackgroundCI electrode array selection can be influenced by measuring the CDL, which is estimated based on the length of the line that connects the round window and the lateral wall of the cochlea when passing through the modiolus. CDL measurement remains time consuming and inter-observer variability has not been studied.MethodsWe evaluate an automatic approach to directly measure the two-turn (2T) CDL using existing algorithms for localizing cochlear anatomy in computed tomography (CT). Pre-op CT images of 309 ears were evaluated. Two fellowship-trained neurotologists manually and independently measured CDL. Inter-observer variability between measurements across expert and automatic observers is assessed. Inter-observer differences for choice of electrode type are also investigated.ResultsManual measurement of CDL by experts tends to underestimate cochlea size and has high inter-observer variability, with mean absolute differences between expert CDL estimations of 1.15 mm. Our results show that this can lead to a large number of cochleae for which a different electrode array type would be selected by different observers, depending on the specific threshold value of CDL used to decide between array type.ConclusionChoosing the best CI electrode array is an important task for optimizing hearing outcomes. Manual cochleae length measurements are user-dependent, and errors impact upon the CI electrode array choice for certain patients. Measuring cochlea length automatically is less time consuming and generates more repeatable results. Our automatic approach could make use of CDL for patient-customized treatment more clinically adoptable.
| S-EPMC5335919 | biostudies-literature
Project description:Objective.Intracortical brain interfaces are an ever evolving technology with growing potential for clinical and research applications. The chronic tissue response to these devices traditionally has been characterized by glial scarring, inflammation, oxidative stress, neuronal loss, and blood-brain barrier disruptions. The full complexity of the tissue response to implanted devices is still under investigation.Approach.In this study, we have utilized RNA-sequencing to identify the spatiotemporal gene expression patterns in interfacial (within 100µm) and distal (500µm from implant) brain tissue around implanted silicon microelectrode arrays. Naïve, unimplanted tissue served as a control.Main results.The data revealed significant overall differential expression (DE) in contrasts comparing interfacial tissue vs naïve (157 DE genes), interfacial vs distal (94 DE genes), and distal vs naïve tissues (21 DE genes). Our results captured previously characterized mechanisms of the foreign body response, such as astroglial encapsulation, as well as novel mechanisms which have not yet been characterized in the context of indwelling neurotechnologies. In particular, we have observed perturbations in multiple neuron-associated genes which potentially impact the intrinsic function and structure of neurons at the device interface. In addition to neuron-associated genes, the results presented in this study identified significant DE in genes which are associated with oligodendrocyte, microglia, and astrocyte involvement in the chronic tissue response.Significance. The results of this study increase the fundamental understanding of the complexity of tissue response in the brain and provide an expanded toolkit for future investigation into the bio-integration of implanted electronics with tissues in the central nervous system.
| S-EPMC8650570 | biostudies-literature
Project description:Electrode microorganism Raw sequence reads
| PRJNA667308 | ENA
Project description:ObjectivesThe goal was to investigate the relationship between the insertion angle/cochlear coverage of cochlear implant electrode arrays and post-operative speech recognition scores in a large cohort of patients implanted with lateral wall electrode arrays.MethodsPre- and post-operative cone beam computed tomography scans of 154 ears implanted with lateral wall electrode arrays were evaluated. Traces of lateral wall and electrode arrays were combined into a virtual reconstruction of the implanted cochlea. This reconstruction was used to measure insertion angles and proportional cochlear coverage. Word recognition scores and sentence recognition scores measured 12 months after implantation using electric-only stimulation were used to examine the relationship between cochlear coverage/insertion angle and implantation outcomes.ResultsPost-operative word recognition scores and the difference between post- and pre-operative word recognition scores were positively correlated with both cochlear coverage and insertion angle, however sentence recognition scores were not. A group-wise comparison of word recognition scores revealed that patients with cochlear coverage below 70% performed significantly worse than patients with coverage between 79%-82% (p = 0.003). Performance of patients with coverage above 82% was on average poorer than between 79%-82, although this finding was not statistically significant (p = 0.84). Dividing the cohort into groups based on insertion angle quadrants revealed that word recognition scores were highest above 450° insertion angle, sentence recognition scores were highest between 450° and 630° and the difference between pre- and post-operative word recognition scores was largest between 540° and 630°, however none of these differences reached statistical significance.ConclusionsThe results of this study show that cochlear coverage has an effect on post-operative word recognition abilities and the benefit patients receive from their implant. Generally, higher coverage led to better outcomes, however there were results indicating that insertion past 82% cochlear coverage may not provide an additional benefit for word recognition. These findings can be useful for choosing the optimal electrode array and thereby improving cochlear implantation outcomes on a patient-individual basis.
| S-EPMC10337941 | biostudies-literature
Project description:The cochlea, a sensitive biosensor, detects sound waves and converts them into electrical signals the brain recognizes as sound. Damage to cochlear hair cells can release proteins, triggering biological responses that may impair hearing. Mass spectrometry-based proteomics offers insights into protein expression changes in cochlear tissues, improving our understanding of inner ear diseases. In this study, we performed a comprehensive proteomics analysis of whole cochlear tissue extracted from healthy guinea pigs and rats. The study optimized protein extraction protocols and analyzed cochlear protein expression using three biological replicates for each animal model. This work optimized protein extraction protocols and analyzed cochlear protein expression using three biological replicates for each animal model. The results identified 1801 proteins in guinea pigs and 3867 proteins in rats, with a high overlap in cochlear protein expression between the left and right ears—93% in guinea pigs and 89% in rats. The findings validate the assumption that the cochlear tissues from both sides of the ears can be considered biologically equivalent. This experiment provides a comprehensive cochlear proteome for guinea pigs and rats, supporting future studies on inner ear disorders.
2025-07-21 | PXD059025 | Pride