Shankai Yin

Ribbon Synapse Plasticity in the Cochleae of Guinea Pigs after Noise-Induced Silent Damage

Noise exposure at low levels or low doses can damage hair cell afferent ribbon synapses without causing permanent threshold shifts. In contrast to reports in the mouse cochleae, initial damage to ribbon synapses in the cochleae of guinea pigs is largely repairable. In the present study, we further investigated the repair process in ribbon synapses in guinea pigs after similar noise exposure. In the control samples, a small portion of afferent synapses lacked synaptic ribbons, suggesting the co-existence of conventional no-ribbon and ribbon synapses. The loss and recovery of hair cell ribbons and post-synaptic densities (PSDs) occurred in parallel, but the recovery was not complete, resulting in a permanent loss of less than 10% synapses. During the repair process, ribbons were temporally separated from the PSDs. A plastic interaction between ribbons and postsynaptic terminals may be involved in the reestablishment of synaptic contact between ribbons and PSDs, as shown by location changes in both structures. Synapse repair was associated with a breakdown in temporal processing, as reflected by poorer responses in the compound action potential (CAP) of auditory nerves to time-stress signals. Thus, deterioration in temporal processing originated from the cochlea. This deterioration developed with the recovery in hearing threshold and ribbon synapse counts, suggesting that the repaired synapses had deficits in temporal processing.

Over-expression of X-linked inhibitor of apoptosis protein slows presbycusis in C57BL/6J mice.

Apoptosis of cochlear cells plays a significant role in age-related hearing loss or presbycusis. In this study, we evaluated whether over-expression of the anti-apoptotic protein known as X-linked Inhibitor of Apoptosis Protein (XIAP) slows the development of presbycusis. We compared the age-related hearing loss between transgenic (TG) mice that over-express human XIAP tagged with 6-Myc (Myc-XIAP) on a pure C57BL/6J genetic background with wild-type (WT) littermates by measuring auditory brainstem responses. The result showed that TG mice developed hearing loss considerably more slowly than WT littermates, primarily within the high-frequency range. The average total hair cell loss was significantly less in TG mice than WT littermates. Although levels of Myc-XIAP in the ear remained constant at 2 and 14 months, there was a marked increase in the amount of endogenous XIAP from 2 to 14 months in the cochlea, but not in the brain, in both genotypes. These results suggest that XIAP over-expression reduces age-related hearing loss and hair cell death in the cochlea.

Silent damage of noise on cochlear afferent innervation in guinea pigs and the impact on temporal processing

Noise-exposure at levels low enough to avoid a permanent threshold shift has been found to cause a massive, delayed degeneration of spiral ganglion neurons (SGNs) in mouse cochleae. Damage to the afferent innervation was initiated by a loss of synaptic ribbons, which is largely irreversible in mice. A similar delayed loss of SGNs has been found in guinea pig cochleae, but at a reduced level, suggesting a cross-species difference in SGN sensitivity to noise. Ribbon synapse damage occurs “silently” in that it does not affect hearing thresholds as conventionally measured, and the functional consequence of this damage is not clear. In the present study, we further explored the effect of noise on cochlear afferent innervation in guinea pigs by focusing on the dynamic changes in ribbon counts over time, and resultant changes in temporal processing. It was found that (1) contrary to reports in mice, the initial loss of ribbons largely recovered within a month after the noise exposure, although a significant amount of residual damage existed; (2) while the response threshold fully recovered in a month, the temporal processing continued to be deteriorated during this period.

Effect of continuous positive airway pressure on lipid profile in patients with obstructive sleep apnea syndrome: A meta-analysis of randomized controlled trials

BACKGROUND Obstructive sleep apnea syndrome (OSAS) is an independent risk factor for development of dyslipidemia. Continuous positive airway pressure (CPAP) is the first-line treatment for OSAS. However, it is unclear whether CPAP improves lipid metabolism. OBJECTIVES To review the effect of CPAP on lipid profile of patients with OSAS. METHODS We searched PubMed, Embase, and the Cochrane Library to identify eligible articles published prior to October 30, 2013. Six randomized controlled trials (RCTs) were subjected to meta-analysis using Comprehensive Meta-Analysis software. RESULTS Six RCTs meeting the inclusion criteria were enrolled. The total numbers of measurements of total cholesterol (TC), triglyceride (TG), low-density lipoprotein (LDL) cholesterol, and high-density lipoprotein (HDL) cholesterol, in CPAP intervention patients and sham/control groups, were 370 and 371, 330 and 328, 276 and 274, and 269 and 266 respectively. The pooled estimate of the difference in the mean TC level between the CPAP and sham CPAP/control groups was significantly different (-0.15 [95% confidence interval, -0.27 to -0.03]; p = 0.01). Subgroup analysis revealed that OSAS patients of younger age, who were more obese, and who had been treated via CPAP for a longer duration, showed a significant decrease in TC levels (the differences in the means were -0.27, -0.24, and -0.20; and the p values 0.001, 0.01, and 0.04, respectively). CONCLUSION We confirmed that CPAP decreases the TC level, especially in OSAS patients who are younger, more obese, and who use CPAP for a longer period. CPAP did not alter TG, LDL, or HDL levels, suggesting that CPAP may have no clinically important effect on lipid metabolism.

Efficient cochlear gene transfection in guinea-pigs with adeno-associated viral vectors by partial digestion of round window membrane

The auditory portion of the inner ear, the cochlea, is an ideal organ for local gene transfection owing to its relative isolation. Various carriers have been tested for cochlear gene transfection. To date, viral vectors appear to have much higher transfection efficacy than non-viral mechanisms. Among these vectors, recombinant adeno-associated virus (rAAV) vectors have several advantages such as being non-pathogenic and the ability to produce prolonged gene expression in various cell types. However, rAAV vectors cannot pass through the intact round window membrane (RWM), otherwise a very attractive approach to access the human inner ear. In this study, performed in guinea-pigs, we describe a method to increase the permeability of RWM to rAAV vectors by partial digestion with collagenase solution. Elevated delivery of rAAV across the partially digested RWM increased transfection efficacy to a satisfactory level, even though it was still lower than that achieved by direct cochleostomy injection. Functional tests (auditory brainstem responses) showed that this enzymatic manipulation did not cause permanent hearing loss if applied appropriately. Morphological observations suggested that the damage to RWM caused by partial digestion healed within four weeks. Taken together, these findings suggest that partial digestion of the RWM is a safe and effective method for increasing the transfection of cochlear sensory cells with rAAV.

Is duration tuning a transient process in the inferior colliculus of guinea pigs

Duration selectivity appears to be a fundamental neural encoding mechanism found throughout the animal kingdom. Previous studies reported that band-pass duration-tuned neurons typically show offset responses and occupy a small portion of auditory neurons in non-echolocation mammals relative to echolocation bats. Therefore, duration tuning is generally weaker in non-echolocation mammals. In the present study, duration tuning was analyzed for 207 neurons recorded in the inferior colliculus (IC) of guinea pigs. Duration tuning was found to be stronger in the onset component of the responses from sustained, on-off and pause neurons than had been reported previously, when a short analysis window was applied. The need for an appropriate time window for duration tuning analysis was also supported by the fact that the on and off responses from an on-off neuron may show different duration tuning features. Therefore, duration tuning appears to be a transient neural coding process in the IC of guinea pigs. Duration tuning for these types of neurons may have been blurred by the use of a relatively unselective, long window.

Coding deficits in hidden hearing loss induced by noise: the nature and impacts

Hidden hearing refers to the functional deficits in hearing without deterioration in hearing sensitivity. This concept is proposed based upon recent finding of massive noise-induced damage on ribbon synapse between inner hair cells (IHCs) and spiral ganglion neurons (SGNs) in the cochlea without significant permanent threshold shifts (PTS). Presumably, such damage may cause coding deficits in auditory nerve fibers (ANFs). However, such deficits had not been detailed except that a selective loss of ANFs with low spontaneous rate (SR) was reported. In the present study, we investigated the dynamic changes of ribbon synapses and the coding function of ANF single units in one month after a brief noise exposure that caused a massive damage of ribbon synapses but no PTS. The synapse count and functional response measures indicates a large portion of the disrupted synapses were re-connected. This is consistent with the fact that the change of SR distribution due to the initial loss of low SR units is recovered quickly. However, ANF coding deficits were developed later with the re-establishment of the synapses. The deficits were found in both intensity and temporal processing, revealing the nature of synaptopathy in hidden hearing loss.

Overexpression of X-linked inhibitor of apoptosis protein protects against noise-induced hearing loss in mice

Apoptosis is responsible for cochlear cell death induced by noise. Here, we show that transgenic (TG) mice that overexpress X-linked inhibitor of apoptosis protein (XIAP) under control of the ubiquitin promoter display reduced hearing loss and cochlear damage induced by acoustic overstimulation (125 dB sound pressure level, 6 h) compared with wild-type (WT) littermates. Hearing status was evaluated using the auditory brainstem response (ABR), whereas cochlear damage was assessed by counts of surviving hair cells (HCs) and spiral ganglion neurons (SGNs) as well as their fibers to HCs. Significantly smaller threshold shifts were found for TG mice than WT littermates. Correspondingly, the TG mice also showed a reduced loss of HCs, SGNs and their fibers to HCs. HC loss was limited to the basal end of the cochlea that detects high frequency sound. In contrast, the ABRs demonstrated a loss of hearing sensitivity across the entire frequency range tested (2–32 kHz) indicating that the hearing loss could not be fully attributed to HC loss alone. The TG mice displayed superior hearing sensitivity over this whole range, suggesting that XIAP overexpression reduces noise-induced hearing loss not only by protecting HCs but also other components of the cochlea.

Tonsillectomy versus Tonsillotomy for Sleep-Disordered Breathing in Children: A Meta Analysis

Objectives Tonsillotomy has gained popular acceptance as an alternative to the traditional tonsillectomy in the management of sleep-disordered breathing in children. Many studies have evaluated the outcomes of the two techniques, but uncertainty remains with regard to the efficacy and complications of tonsillotomy versus a traditional tonsillectomy. This study was designed to investigate the efficacy and complications of tonsillotomy versus tonsillectomy, in terms of the short- and long-term results. Methods We collected data from electronic databases including MEDLINE, EMBASE, and the Cochrane Library. The following inclusion criteria were applied: English language, children, and prospective studies that directly compared tonsillotomy and tonsillectomy in the management of sleep disordered breathing. Subgroup analysis was then performed. Results In total, 10 eligible studies with 1029 participants were included. Tonsillotomy was shown to be advantageous over tonsillectomy in short-term measures, such as a lower hemorrhage rate, shorter operation time, and faster pain relief. In long-term follow-up, there was no significant difference in resolution of upper-airway obstructive symptoms, the quality of life, or postoperative immune function between the tonsillotomy and tonsillectomy groups. The risk ratio of SDB recurrence was 3.33 (95% confidence interval = 1.62 6.82, P = 0.001), favoring tonsillectomy at an average follow-up of 31 months. Conclusions Tonsillotomy may be advantageous over tonsillectomy in the short term measures and there are no significant difference of resolving obstructive symptoms, quality of life and postoperative immune function. For the long run, the dominance of tonsillotomy may be less than tonsillectomy with regard to the rate of sleep-disordered breathing recurrence.

Local inhibition shapes duration tuning in the inferior colliculus of guinea pigs

Neural tuning to sound durations is a useful filter for the identification of a variety of sounds. Previous studies have shown that the interaction between excitatory and inhibitory inputs plays a role in duration selectivity in echolocating bats. However, this has not been investigated in non-echolocating mammals. In the inferior colliculus (IC) of these mammals, it is recognized that the excitatory responses to sounds are mediated through AMPA and NMDA receptors while the inhibitory input is mediated through gamma-aminobutyric acid (GABA) and glycine receptors. The present study explores the potential interplay between inhibitory and excitatory inputs and its role in the duration selectivity of IC neurons in guinea pigs. It was found that the application of bicuculline (BIC, a GABA A blocker) and/or strychnine (STRY, a glycine blocker) eliminated or reduced duration tuning in most units that were duration tuned (32 out of 39 for BIC, 50 out of 64 for STRY, respectively). The inhibitory input (either by GABA or by glycine) appeared to have a stronger regulating effect on the early excitation mediated by AMPA than on later excitation by NMDA. This is more distinguishable in neurons that show duration selectivity. In conclusion, the inhibitory effect on the early responses appears to be the main contributor for the duration selectivity of the IC in guinea pigs; potential mechanisms for this duration selectivity are also discussed.