ACOUSTIC CROSS-OVER BETWEEN THE EARS IN MICE (Mus musculus) DETERMINED USING A NOVEL ABR BASED BIO-ASSAY

ABSTRACT Closed-field stimulation of one ear, at high sound intensity, will activate both ears because of bone/soft tissue transmission of the acoustic signal across the skull. In human psychophysics and in clinical audiometry a knowledge of interaural attenuation values is important, particularly when assessing asymmetrical hearing loss or in studies of monaural hearing. Similarly, in testing monaural hearing in experimental animal studies, acoustic cross-over can result in erroneous conclusions about hearing function. The mouse has become a widely used animal model for various types of hearing loss, especially those relating to gene mutations, and also for age related deafness (presbycusis). In the present study we have measured acoustic cross-over in this species using a novel bio-assay technique based on auditory brainstem evoked responses (ABR). We report here for the mouse, an interaural attenuation of 37-45dB for click and 32kHz toneburst SOMMAIRE La stimulation de l'oreille unique à haute intensité sonore, en sphère fermée, cause l'activation des deux oreilles dù à la transmission du signal acoustique a travers les tissus mous et l'os du crâne. En psychophysique de l'homme et l'audiométrie clinique, l'atténuation interaural doit être connue dans les études d'audience mono ou de la surdité asymétrique. De même, pour tester l'audition monaurale dans les études expérimentales chez les animaux, la transmission trans-crânienne (aguillage acoustique) peut produire des conclusions erronées au sujet de la fonction auditive. La souris est devenue le modèle animal largement utilisé pour différents types de pertes auditives, en particulier celles qui ont a trait à des mutations géniques, et aussi de la surdité liée à l'âge (presbyacousie). Dans l'étude en question, nous avons mesuré la transmission trans-crânienne (aguillage acoustique) chez cette espèce en utilisant une technique de dosage biologique basée sur les potentiels évoqués auditifs (PEA). Nous rapportons ici chez la souris, une atténuation interaural de 37-45dB pour le clic et le 32kHz pip tonal

DIP/WISH deficiency enhances synaptic function and performance in the Barnes maze

<p>Abstract</p> <p>Background</p> <p>DIP (diaphanous interacting protein)/WISH (WASP interacting SH3 protein) is a protein involved in cytoskeletal signaling which regulates actin cytoskeleton dynamics and/or microtubules mainly through the activity of Rho-related proteins. Although it is well established that: 1) spine-head volumes change dynamically and reflect the strength of the synapse accompanying long-term functional plasticity of glutamatergic synaptic transmission and 2) actin organization is critically involved in spine formation, the involvement of DIP/WISH in these processes is unknown.</p> <p>Results</p> <p>We found that DIP/WISH-deficient hippocampal CA1 neurons exhibit enhanced long-term potentiation via modulation of both pre- and post-synaptic events. Consistent with these electrophysiological findings, DIP/WISH-deficient mice, particularly at a relatively young age, found the escape hole more rapidly in the Barnes maze test.</p> <p>Conclusions</p> <p>We conclude that DIP/WISH deletion improves performance in the Barnes maze test in mice probably through increased hippocampal long-term potentiation.</p

Early Enzyme Replacement Therapy Improves Hearing and Immune Defects in Adenosine Deaminase Deficient-Mice

Background: Inherited defects in adenosine deaminase (ADA) cause severe immune deficiency, which can be corrected by ADA enzyme replacement therapy (ERT). Additionally, ADA-deficient patients suffer from hearing impairment. We hypothesized that ADA-deficient (–/–) mice also exhibit hearing abnormalities and that ERT from an early age will improve the hearing and immune defects in these mice.Methods: Auditory brainstem evoked responses, organ weights, thymocytes numbers, and subpopulations, lymphocytes in peripheral blood as well as T lymphocytes in spleen were analyzed in ADA–/– and ADA-proficient littermate post-partum (pp). The cochlea was visualized by scanning electron microscopy (SEM). The effects of polyethylene glycol conjugated ADA (PEG-ADA) ERT or 40% oxygen initiated at 7 days pp on the hearing and immune abnormalities were assessed.Results: Markedly abnormal hearing thresholds responses were found in ADA–/– mice at low and medium tone frequencies. SEM demonstrated extensive damage to the cochlear hair cells of ADA–/– mice, which were splayed, short or missing, correlating with the hearing deficits. The hearing defects were not reversed when hypoxia in ADA–/– mice was corrected. Progressive immune abnormalities were detected in ADA–/– mice from 4 days pp, initially affecting the thymus followed by peripheral lymphocytes and T cells in the spleen. ERT initiated at 7 days pp significantly improved the hearing of ADA–/– mice as well as the number of thymocytes and T lymphocytes, although not all normalized.Conclusions: ADA deficiency is associated with hearing deficits and damage to cochlear hair cells. Early initiation of ERT improves the hearing and immune abnormalities

Resting Neural Activity Patterns in Auditory Brain Areas following Conductive Hearing Loss

Conductive hearing loss (otitis media) in young children can effect speech and language development. However, little is known about the effects of conductive loss on neural activity in the auditory system. Hypothesis: Conductive hearing loss will change resting activity levels at the inner hair cell synapse, and lead to auditory deprivation of central auditory pathways. A conductive loss was produced by blocking the ear canals in mice. Resting neural activity patterns were quantified in brainstem and midbrain using c-fos immuno-labelling. Experimental subjects were compared to normal hearing controls and subjects with cochlear ablation. Conductive loss subjects showed a trend in reduction in c-fos labelled cells in cochlear nucleus and the central nucleus of inferior colliculus compared to normal controls. Results seen in this study may indicate the influence of conductive hearing loss on the developing auditory brain during early postnatal years when the system is highly plastic.MAS

Ultrasonic bone removal from the ossicular chain affects cochlear structure and function

Abstract Introduction Ultrasonic bone removal devices (UBD) are capable of cutting through bony tissue without injury to adjacent soft tissue. The feasibility and safety of using this technology for removal of bone from an intact ossicular chain (as might be required for otosclerosis or congenital fixation) was investigated in an animal model. Methods This was a prospective animal study conducted on seven anesthetised adult chinchillas. An UBD was used to remove bone from the malleus head in situ. Pre and post-operative distortion product otoacoustic emission (DPOAE) levels and auditory brainstem response (ABR) thresholds were recorded. Scanning electron microscopy (SEM) was used to assess cochlear haircell integrity. Results Precise removal of a small quantity of bone from the malleus head was achieved by a 30s application of UBD without disruption of the ossicular chain or tympanic membrane. DPOAEs became undetectable after the intervention with signal-to-noise ratios (SNR)  85 dB SPL in 13 ears. SEM showed significant disruption of structural integrity of the organ of Corti, specifically loss and damage of outer haircells. Conclusions Although UBD can be used to reshape an ossicle without middle ear injury, prolonged contact with the ossicular chain can cause structural and functional injury to the cochlea. Extensive cochlea pathology was found, but we did not investigate for recovery from any temporary threshold shift. In the authors’ opinion, further study should be undertaken before consideration is given to use of the device for release of ossicular fixation. Graphical abstrac

Surgical Considerations for an Osseointegrated Steady State Implant (OSIA2®) in Children

Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/172349/1/lary29892_am.pdfhttp://deepblue.lib.umich.edu/bitstream/2027.42/172349/2/lary29892.pd

Attenuating Cardiac Pulsations within the Cochlea: Structure and Function of Tortuous Vessels Feeding Stria Vascularis

The mammalian ear has an extraordinary capacity to detect very low-level acoustic signals from the environment. Sound pressures as low as a few μPa (−10 dB SPL) can activate cochlear hair cells. To achieve this sensitivity, biological noise has to be minimized including that generated by cardiovascular pulsation. Generally, cardiac pressure changes are transmitted to most peripheral capillary beds; however, such signals within the stria vascularis of the cochlea would be highly disruptive. Not least, it would result in a constant auditory sensation of heartbeat. We investigate special adaptations in cochlear vasculature that serve to attenuate cardiac pulse signals. We describe the structure of tortuous arterioles that feed stria vascularis as seen in corrosion casts of the cochlea. We provide a mathematical model to explain the role of this unique vascular anatomy in dampening pulsatile blood flow to the stria vascularis.Peer Reviewe

Corrosion casting of the subglottis following endotracheal tube intubation injury: a pilot study in Yorkshire piglets

Abstract Purpose Subglottic stenosis can result from endotracheal tube injury. The mechanism by which this occurs, however, is not well understood. The purpose of this study was to examine the role of angiogenesis, hypoxia and ischemia in subglottic mucosal injury following endotracheal intubation. Methods Six Yorkshire piglets were randomized to either a control group (N=3, ventilated through laryngeal mask airway for corrosion casting) or accelerated subglottic injury group through intubation and induced hypoxia as per a previously described model (N=3). The vasculature of all animals was injected with liquid methyl methacrylate. After polymerization, the surrounding tissue was corroded with potassium hydroxide. The subglottic region was evaluated using scanning electron microscopy looking for angiogenic and hypoxic or degenerative features and groups were compared using Mann–Whitney tests and Friedman’s 2-way ANOVA. Results Animals in the accelerated subglottic injury group had less overall angiogenic features (P=.002) and more overall hypoxic/degenerative features (P=.000) compared with controls. Amongst angiogenic features, there was decreased budding (P=.000) and a trend toward decreased sprouting (P=.037) in the accelerated subglottic injury group with an increase in intussusception (P=.004), possibly representing early attempts at rapid revascularization. Amongst hypoxic/degenerative features, extravasation was the only feature that was significantly higher in the accelerated subglottic injury group (P=.000). Conclusions Subglottic injury due to intubation and hypoxia may lead to decreased angiogenesis and increased blood vessel damage resulting in extravasation of fluid and a decreased propensity toward wound healing in this animal model