Haibo Shi

Triple semicircular canal occlusion for the treatment of Meniere's disease

Conclusion. Triple semicircular canal occlusion (TSCO) controls vertigo, is easy to perform, and could be used as an alternative procedure for the treatment of Ménières disease in selected patients who complain mainly of intractable vertigo. Objective. To seek an effective alternative surgical procedure for treating Ménières disease in selected patients with intolerant rotational vertigo. Patients and methods. Three patients with Ménières disease who underwent unsuccessful endolymphatic sac decompression or mastoid shunt, then underwent TSCO. Vertigo control and vestibular and auditory function were measured. Results. The early vestibular symptoms caused by surgery resolved quickly and no hearing deterioration occurred after surgery. At the end of the follow-up period, based on the AAO-HNS criteria, two cases had complete control of vertigo (class A) and the other had substantial control of vertigo attacks (class B). Hearing was similar to the preoperative level at the end of the follow-up period.

Mechanisms underlying taurine protection against glutamate-induced neurotoxicity.

Taurine appears to exert potent protections against glutamate (Glu)-induced injury to neurons, but the underlying molecular mechanisms are not fully understood. The possibly protected targets consist of the plasma membrane and the mitochondrial as well as endoplasmic reticulum (ER) membranes. Protection may be provided through a variety of effects, including the prevention of membrane depolarization, neuronal excitotoxicity and mitochondrial energy failure, increases in intracellular free calcium ([Ca2+]i), activation of calpain, and reduction of Bcl-2 levels. These activities are likely to be linked spatially and temporally in the neuroprotective functions of taurine. In addition, events that occur downstream of Glu stimulation, including altered enzymatic activities, apoptotic pathways, and necrosis triggered by the increased [Ca2+]i, can be inhibited by taurine. This review discusses the possible molecular mechanisms of taurine against Glu-induced neuronal injury, providing a better understanding of the protective processes, which might be helpful in the development of novel interventional strategies.

Bilirubin induces auditory neuropathy in neonatal guinea pigs via auditory nerve fiber damage

Bilirubin can cause temporary or permanent sensorineural deafness in newborn babies with hyperbilirubinemia. However, the underlying targets and physiological effects of bilirubin‐induced damage in the peripheral auditory system are unclear. Using cochlear functional assays and electron microscopy imaging of the inner ear in neonatal guinea pigs, we show here that bilirubin exposure resulted in threshold elevation in both compound action potential (CAP) and auditory brainstem response (ABR), which was apparent at 1 hr and peaked 8 hr after drug administration. The threshold elevation was associated with delayed wave latencies and elongated interwave intervals in ABR and CAP. At 72 hr postinjection, these measures returned to control levels, except for the CAP amplitude. Cochlear microphonics remained unchanged during the experiment. Morphological abnormalities were consistent with the electrophysiological dysfunction, revealing fewer auditory nerve fibers (ANFs) in the basal turn, myelin sheath lesions of spiral ganglion neurons (SGNs) and ANFs, and loss of type 1 afferent endings beneath inner hair cells (IHCs) without loss of hair cells at 8 hr posttreatment. Similar to the electrophysiological findings, morphological changes were mostly reversed 10 days after treatment, except for the ANF reduction in the basal turn. These results suggest that hyperbilirubinemia in neonatal guinea pigs impaired auditory peripheral neuromechanisms that targeted mainly the IHC synapses and the myelin sheath of SGNs and their fibers. Our observations indicate a potential connection between hyperbilirubinemia and auditory neuropathy.

Interaction between taurine and GABAA/glycine receptors in neurons of the rat anteroventral cochlear nucleus

Taurine, one of the most abundant endogenous amino acids in the mammalian central nervous system (CNS), is involved in neural development and many physiological functions. In this study, the interaction between taurine and GABA(A)/glycine receptors was investigated in young rat (P13-P15) anteroventral cochlear nucleus (AVCN) neurons using the whole-cell patch-clamp method. We found that taurine at low (0.1mM) and high (1mM) concentrations activated both GABA(A) and glycine receptors, but not AMPA and NMDA receptors. The reversal potentials of taurine-, GABA- or glycine-evoked currents were close to the expected chloride equilibrium potential, indicating that receptors activated by these agonists were mediating chloride conductance. Moreover, our results showed that the currents activated by co-application of GABA and glycine were cross-inhibitive. Sequential application of GABA and glycine or vice versa also reduced the glycine or GABA evoked currents. There was no cross-inhibition when taurine and GABA or taurine and glycine were applied simultaneously, but the response was larger than that evoked by GABA or glycine alone. These results suggest that taurine can serve as a neuromodulator to strengthen GABAergic and glycinergic neurotransmission in the rat AVCN.

Comparative study of the efficacy of the canalith repositioning procedure versus the vertigo treatment and rehabilitation chair

Abstract Conclusion: Vertigo treatment and rehabilitation chair (TRV) may be suggested as the first choice for patients with posterior canal benign paroxysmal positional vertigo (p-BPPV). Objective: To investigate the short- and long-term treatment efficacy of the canalith repositioning procedure (CRP) versus TRV for patients with p-BPPV. Methods: A total of 165 patients with unilateral p-BPPV were assigned to either the CRP group or the TRV group. Patients were assessed at 1 week, 4 weeks, 3 months, and 6 months after their first treatment. The numbers of treatment sessions required for successful repositioning in both groups at 4 weeks, 3 months, and 6 months were recorded. Results: Treatment efficacy of patients in the TRV group was significantly better than that of patients in the CRP group 1 week after the first treatment. The number of treatment sessions needed for successful repositioning was significantly lower in the TRV group than in the CRP group at 4 weeks and 3 months after the first treatment.

Bilirubin enhances neuronal excitability by increasing glutamatergic transmission in the rat lateral superior olive.

Hyperbilirubinemia is one of the most common clinical phenomena observed in human newborns. To achieve effective therapeutic treatment, numerous studies have been done to determine the molecular mechanisms of bilirubin-induced neuronal excitotoxicity. However, there is no conclusive evidence for the involvement of glutamatergic synaptic transmission in bilirubin-induced neuronal hyperexcitation and excitotoxicity. In the present study, using gramicidin-perforated patch-clamp techniques, spontaneous excitatory postsynaptic currents (sEPSCs) were recorded from lateral superior olive (LSO) neurons isolated from postnatal 11-14-day-old (P11-14) rats. The application of 3 μM bilirubin increased the frequency, but not the amplitude, of sEPSCs. The action of bilirubin was tetrodotoxin (TTX)-insensitive, as bilirubin also increased the frequency, but not the amplitude, of mEPSCs. The amplitudes of GABA-activated (I(GABA)) and glutamate-activated (I(glu)) currents were not affected by bilirubin. Under current-clamp conditions, no spontaneous action potentials were observed in control solution. However, the application of 3 μM bilirubin for 4-6 min evoked a considerable rate of action-potential firing. The evoked firing was partially occluded by D,L-2-amino-5-phosphonovaleric acid (APV), an NMDA receptor antagonist, but completely inhibited by a combination of APV and 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo[f]quinoxaline-2,3-dione (NBQX), an AMPA receptor antagonist. These results indicate that bilirubin facilitates presynaptic glutamate release, enhances glutamatergic synaptic transmission by activating postsynaptic AMPA and NMDA receptors, and leads to neuronal hyperexcitation. This study provides a better understanding of the mechanism of bilirubin-induced excitotoxicity and determines for the first time that both AMPA and NMDA receptors are likely involved in the excitotoxicity produced by bilirubin.

Ontogenetic development of the auditory sensory organ in zebrafish ( Danio rerio ): changes in hearing sensitivity and related morphology

Zebrafish (Danio rerio) is an important model organism in hearing research. However, data on the hearing sensitivity of zebrafish vary across different reports. In the present study, the hearing sensitivity of zebrafish was examined by analysing the auditory evoked potentials (AEPs) over a range of total lengths (TLs) from 12 to 46 mm. Morphological changes in the hair cells (HCs) of the saccule (the main auditory end organ) and their synapses with primary auditory neurons were investigated. The AEPs were detected up to a much higher frequency limit (12 kHz) than previously reported. No significant difference in the frequency response range was observed across the TL range examined. However, the AEP thresholds demonstrated both developmental improvement and age-related loss of hearing sensitivity. The changes in hearing sensitivity were roughly consistent with the morphological changes in the saccule including (1) the number and density of HCs, (2) the organization of stereocilia, and (3) the quantity of a main ribbon protein, Ribeye b. The results of this study established a clear baseline for the hearing ability of zebrafish and revealed that the changes in the saccule contribute to the observed changes in TL (age)-related hearing sensitivity.

Categories of Auditory Performance and Speech Intelligibility Ratings of Early-Implanted Children without Speech Training

Objective To assess whether speech therapy can lead to better results for early cochlear implantation (CI) children. Patients A cohort of thirty-four congenitally profoundly deaf children who underwent CI before the age of 18 months at the Sixth Hospital affiliated with Shanghai Jiaotong University from January 2005 to July 2008 were included. Nineteen children received speech therapy in rehabilitation centers (ST), whereas the remaining fifteen cases did not (NST), but were exposed to the real world, as are normal hearing children. Methods All children were assessed before surgery and at 6, 12, and 24 months after surgery with the Categories of Auditory Performance test (CAP) and the Speech Intelligibility Rating (SIR). Each assessment was given by the same therapist who was blind to the situation of the child at each observation interval. CAP and SIR scores of the groups were compared at each time point. Results Our study showed that the auditory performance and speech intelligibility of trained children were almost the same as to those of untrained children with early implantation. The CAP and SIR scores of both groups increased with increased time of implant use during the follow-up period, and at each time point, the median scores of the two groups were about equal. Conclusions These results indicate that great communication benefits are achieved by early implantation (<18 months) without routine speech therapy. The results exemplify the importance of enhanced social environments provided by everyday life experience for human brain development and reassure parents considering cochlear implants where speech training is unavailable.

Protein kinase A and C signaling induces bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus neurons.

Previous studies have suggested that bilirubin can potentiate GABA/glycinergic synaptic transmission in lateral superior olivary nucleus neurons, but the cellular mechanism has not been defined. The present study evaluated the possible roles of protein kinase A (PKA) and C (PKC) in bilirubin potentiation of GABA/glycinergic synaptic transmission in rat ventral cochlear nucleus (VCN) neurons. VCN neurons were acutely isolated from postnatal 10-12-day-old (P10-12) rats and were voltage-clamped in whole-cell mode. Miniature inhibitory postsynaptic currents (mIPSC) frequencies, but not amplitude, were increased by bilirubin. Forskolin (PKA activator) and H-89 (PKA inhibitor) also individually increased mIPSCs frequency, with an additional increase induced by co-incubation with bilirubin and H-89. Pretreatment with forskolin blocked bilirubin potentiation. mIPSC frequency was not altered by phorbol 12,13-diacetate (PKC activator), but mIPSC frequency was increased following co-application of bilirubin. The mIPSC frequency was increased by chelerythrine (PKC inhibitor), and then further increased after the addition of bilirubin. Neither H-89, forskolin, nor PDA, nor their co-application with bilirubin affected mIPSC amplitudes of GABA-activated (I(GABA))/glycine-activated (I(gly)) currents, suggesting a presynaptic locus of activity. Chelerythrine decreased the mIPSC amplitudes and I(GABA)/I(gly), suggesting a postsynaptic locus of activity. These data suggest that both PKA and PKC can modulate GABA and glycine release in rat VCN neurons. Bilirubin facilitates transmitter release via presynaptic PKA activation, which might provide insight into the cellular mechanism underlying bilirubin-induced hearing dysfunction.

Minocycline cannot protect neurons against bilirubin-induced hyperexcitation in the ventral cochlear nucleus

Excitotoxicity has been suggested to play an important role in many central nervous system diseases, particularly in bilirubin encephalopathy. Minocycline treatment has been proposed to be one of the most promising potential therapies for excitotoxicity-induced neurological disorders. However, some key questions, such as the electrophysiological effect of minocycline on neuronal excitability and hyperexcitation in pathological conditions, require clarification. In this study, using patch-clamp techniques, we showed that bilirubin increased the frequency of both spontaneous excitatory postsynaptic currents (sEPSCs) and neuronal firing in isolated ventral cochlear nucleus (VCN) neurons at postnatal days 11-14 (P11-14) in rats but it did not affect the amplitude of sEPSCs or glutamate-activated (I(Glu)) currents. However, minocycline had no effect on sEPSC frequency or I(Glu) amplitude. Furthermore, minocycline pretreatment did not abolish bilirubin-induced sEPSC potentiation or neuron firing. These data suggest that minocycline does not affect excitatory synaptic transmission or hyperexcitation induced by bilirubin in VCN neurons. From these results, we propose that the neuroprotective efficacy of minocycline, if it can protect neurons against neurotoxicity induced by substances like bilirubin, is mediated by either an alternative mechanism or downstream events post neuronal hyperexcitation. Certainly, additional investigation of the neuroprotective effects of minocycline is required before embarking on further clinical trials.