Fibrous tissue growth and loss of residual hearing after cochlear implantation can be reduced by application of the glucocorticoid dexamethasone-21-phosphate-disodium-salt (DEX). To date, sustained delivery of this agent to the cochlea using a number of pharmaceutical technologies has not been entirely successful. In this study we examine a novel way of continuous local drug application into the inner ear using a refillable hydrogel functionalized silicone reservoir. A PEG-based hydrogel made of reactive NCO-sP(EO-stat-PO) prepolymers was evaluated as a drug conveying and delivery system in vitro and in vivo. Encapsulating the free form hydrogel into a silicone tube with a small opening for the drug diffusion resulted in delayed drug release but unaffected diffusion of DEX through the gel compared to the free form hydrogel. Additionally, controlled DEX release over several weeks could be demonstrated using the hydrogel filled reservoir. Using a guinea-pig cochlear trauma model the reservoir delivery of DEX significantly protected residual hearing and reduced fibrosis. As well as being used as a device in its own right or in combination with cochlear implants, the hydrogel-filled reservoir represents a new drug delivery system that feasibly could be replenished with therapeutic agents to provide sustained treatment of the inner ear.
This study aimed to compare the neural correlates of acoustic stimulus representation in the auditory sensory memory on an automatic basis between tinnitus subjects and normal hearing (NH) controls, using topographical maps of the MMNs obtained with the multi-feature paradigm. A new and faster paradigm was adopted to look for differences between 2 groups of subjects. Twenty-eight subjects with chronic subjective idiopathic tinnitus and 33 matched healthy controls were included in the study. Brain electrical activity mapping of multi-feature MMN paradigm was recorded from 32 surface scalp electrodes. Three MMN parameters for five deviants consisting frequency, intensity, duration, location and silent gap were compared between the two groups. The MMN amplitude, latency and area under the curve over a region of interest comprising: F3, F4, Fz, FC3, FC4, FCz, and Cz were computed to provide better signal to noise ratio. These three measures could differentiate the cognitive processing disturbances in tinnitus sufferers. The MMN topographic maps revealed significant differences in amplitude and area under the curve for frequency, duration and silent gap deviants in tinnitus subjects compared to NH controls. The current study provides electrophysiological evidence supporting the theory that the pre-attentive and automatic central auditory processing is impaired in individuals with chronic tinnitus. Considering the advantages offered by the MMN paradigm used here, these data might be a useful reference point for the assessment of sensory memory in tinnitus patients and it can be applied with reliability and success in treatment monitoring.
The present study was performed to examine the impact of the release rate of ciprofloxacin from prostheses coated with nanoporous silica layers on the outcome of an acute bacterial infection of the middle ear of rabbits.
Ultra high viscous (UHV-) alginate is a suitable matrix for brain-derived neurotrophic factor (BDNF) producing cells, enabling cell survival and BDNF release out of the matrix and subsequent protection of auditory neuronal cells.
Bats (Chiroptera) host major human pathogenic viruses including corona-, paramyxo, rhabdo- and filoviruses. We analyzed six different cell lines from either Yinpterochiroptera (including African flying foxes and a rhinolophid bat) or Yangochiroptera (genera Carollia and Tadarida) for susceptibility to infection by different enveloped RNA viruses. None of the cells were sensitive to infection by transmissible gastroenteritis virus (TGEV), a porcine coronavirus, or to infection mediated by the Spike (S) protein of SARS-coronavirus (SARS-CoV) incorporated into pseudotypes based on vesicular stomatitis virus (VSV). The resistance to infection was overcome if cells were transfected to express the respective cellular receptor, porcine aminopeptidase N for TGEV or angiotensin-converting enzyme 2 for SARS-CoV. VSV pseudotypes containing the S proteins of two bat SARS-related CoV (Bg08 and Rp3) were unable to infect any of the six tested bat cell lines. By contrast, viral pseudotypes containing the surface protein GP of Marburg virus from the family Filoviridae infected all six cell lines though at different efficiency. Notably, all cells were sensitive to infection by two paramyxoviruses (Sendai virus and bovine respiratory syncytial virus) and three influenza viruses from different subtypes. These results indicate that bat cells are more resistant to infection by coronaviruses than to infection by paramyxoviruses, filoviruses and influenza viruses. Furthermore, these results show a receptor-dependent restriction of the infection of bat cells by CoV. The implications for the isolation of coronaviruses from bats are discussed.
In the 1970s, Tavolga conducted a series of experiments in which he found behavioral evidence that the vocalizations of the catfish species Ariopsis felis may play a role in a coarse form of echolocation. Based on his findings, he postulated a similar function for the calls of closely related catfish species. Here, we describe the physical characteristics of the predominant call-type of Ariopsis seemanni. In two behavioral experiments, we further explore whether A. seemanni uses these calls for acoustic obstacle detection by testing the hypothesis that the call-emission rate of individual fish should increase when subjects are confronted with novel objects, as it is known from other vertebrate species that use pulse-type signals to actively probe the environment. Audio-video monitoring of the fish under different obstacle conditions did not reveal a systematic increase in the number of emitted calls in the presence of novel objects or in dependence on the proximity between individual fish and different objects. These negative findings in combination with our current understanding of directional hearing in fishes (which is a prerequisite for acoustic obstacle detection) make it highly unlikely that A. seemanni uses its calls for acoustic obstacle detection. We argue that the calls are more likely to play a role in intra- or interspecific communication (e.g. in school formation or predator deterrence) and present results from a preliminary Y-maze experiment that are indicative for a positive phonotaxis of A. seemanni towards the calls of conspecifics.
Sex-specific differences in orientation strategies are well known for several rodent and primate species with females relying more on landmarks when it comes to visually guided orientation, whereas males preferentially use Euclidean cues. We used the echolocating bat Phyllostomus discolor for a behavioural study on gender differences in the use of acoustic landmarks. The experimental animals (6 males, 6 females) had to learn and perform a simple orientational task, firstly in the absence of landmarks and subsequently in the presence of four acoustic landmarks of which one was occasionally removed during the critical experiment. The results presented here show that gender differences in the use of acoustic landmarks exist in P. discolor, which supports our hypothesis that the phenomenon is independent of the modality that is used to sense the environment during orientation. Therefore, our findings allow for the prediction of similar phenomena in other acoustically orienting mammals. Interestingly, due to the specific ecology of P. discolor, our results partially contradict the evolutionary theories on gender-specific orientation, as will be discussed. Finally, we consider our finding as being one of several important steps toward establishing bats as a new model organism in neuroscientific studies on allocentric spatial cognition in mammals.
Topographic cortical representation of echo delay, the cue for target range, is an organizational feature implemented in the auditory cortices of certain bats dedicated to catch flying insects. Such cortical echo-delay maps provide a calibrated neural representation of object spatial distance. To assess general requirements for echo-delay computations, cortical delay sensitivity was examined in the short-tailed fruit bat Carollia perspicillata that uses frequency-modulated (FM) echolocation signals. Delay-tuned neurons with temporal specificity comparable to those of insectivorous bats are located within the high-frequency (HF) field of the auditory cortex. All recorded neurons in the HF field respond well to single pure-tone and FM-FM stimulus pairs. The neurons respond to identical FM harmonic components in echolocation pulse and delayed echo (e.g., FM(2)-FM(2)). Their characteristic delays (CDs) for low echo amplitudes range between 1 and 24 ms, which is comparable to other bat species. Maps of the topography of FM-FM neurons show that they are distributed across the entire HF area and organized along a rostrocaudal echo-delay axis representing object distance. Rostrally located neurons tuned to delays of 2-8 ms are overrepresented (66% of CDs). Neurons with longer delays (>/=10 ms) are located throughout the caudal half of the HF field. The delay-sensitive chronotopic area covers approximately 3.3 mm in rostrocaudal and approximately 3.7 mm in dorsoventral direction, which is comparable or slightly larger than the size of cortical delay-tuned areas in insectivorous constant frequency bats, the only other bat species for which cortical chronotopy has been demonstrated. This indicates that chronotopic cortical organization is not only used exclusively for precise insect localization in constant frequency bats but could also be of advantage for general orientation tasks.
Chronic otitis media is a common disease often accompanied by recurrent bacterial infections. These may lead to the destruction of the middle ear bones such that prostheses have to be implanted to restore sound transmission. Surface coatings with layered double hydroxides (LDHs) are evaluated here as a possibility for drug delivery systems with convenient advantages such as low cytotoxicity and easy synthesis. Male New Zealand White rabbits were implanted with Bioverit(®) II middle ear prostheses coated with the LDH Mg(4)Al(2)(OH)(12)(SO(4))(2)·6H(2)O impregnated with ciprofloxacin. 12 (group 1) were directly infected with Pseudomonas aeruginosa and another 12 (group 2) 1 week after the implantation. Clinical outcome, blood counts, histological analyses and microbiological examination showed an excellent antimicrobial activity for group 1, whereas this effect was attenuated in animals where infection was performed 1 week after implantation. This is the first study to demonstrate an efficient drug delivery system with an LDH coating on prostheses in the middle ear.
Stress exposure evokes a variety of physiological and behavioral responses in an organism, enabling it to cope with stressful situations and changes in the environment. In a previous study, we found that subjecting individuals of Carollia perspicillata to a chronic immobilization stress paradigm resulted in a significant increase of fecal cortisol concentrations. In the present study, we investigated the influence of stress on the behavior of C. perspicillata, by adapting a commonly used behavioral paradigm for characterizing coping styles of animals (i.e., the elevated-plus maze) to bats. Adult bats were subjected 1 h/day to immobilization over a period of 10 days. On the subsequent day, the behavior of each animal was analyzed in a custom-made plus maze, consisting of four arms (two open and two enclosed ones) and designed 3D because of the bats ability to fly. In this newly invented design, we compared the behaviors of stressed animals and controls. Changes in locomotor and exploratory behavior suggest two divergent adaptive behaviors in C. perspicillata following the chronic stress paradigm, possibly indicating different stress coping styles.
The treatment of choice for profound sensorineural hearing loss (SNHL) is direct electrical stimulation of spiral ganglion cells (SGC) via a cochlear implant (CI). The number and excitability of SGC seem to be critical for the success that can be achieved via CI treatment. However, SNHL is associated with degeneration of SGC. Long-term drug delivery to the inner ear for improving SGC survival may be achieved by functionalisation of CI electrodes with cells providing growth factors. Therefore, the capacity of brain-derived neurotrophic factor (BDNF)-secreting NIH3T3 cells grown on cylindrically shaped silicone elastomers (SE) to exert local and sustained neuroprotective effects was assessed in vitro and in vivo. An in vitro model to investigate adhesion and cell growth of lentivirally modified NIH3T3 cells synthesising BDNF on SE was established. The bioactivity of BDNF was characterised by co-cultivation of SGC with cell-coated SE. In addition, cell-coated SE were implanted into deafened guinea pigs. The recombinant NIH3T3 cells proliferated on silicone surfaces during 14 days of cultivation and expressed significantly increasing BDNF levels. Enhanced survival rates and neurite outgrowth of SGC demonstrated the bioactivity of BDNF in vitro. Implantation of SE with adhering BDNF-secreting NIH3T3 cells into the cochleae of systemically deafened guinea pigs induced a significant increase in SGC survival in comparison to SE without cell coating. Our data demonstrate a novel approach of cell-based long-term drug delivery to support SGC survival in vitro and in vivo. This therapeutic strategy--once transferred to cells suitable for clinical application--may improve CI performance.
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