Sulin Zhang

A long-term high-fat diet increases oxidative stress, mitochondrial damage and apoptosis in the inner ear of D-galactose-induced aging rats.

In humans, chronic dyslipidemia associated with elevated triglycerides may reduce auditory function. However, there is little evidence available in the literature concerning the effects of a long-term high-fat diet (HFD) on the inner ears of animals. The purpose of this study was to investigate the effect of 12 month-HFD on the inner ear of Sprague-Dawley rats and on the D-galactose (D-gal)-induced aging process in the inner ear. We found that 12 month-HFD markedly elevated the auditory brainstem response (ABR) threshold in the high-frequency region. The HFD significantly increased the generation of reactive oxygen species (ROS) and the expressions of NADPH oxidase (NOX) and the uncoupling proteins (UCP). Furthermore, an elevated accumulation of the mitochondrial DNA (mtDNA) common deletion (CD) and mitochondrial ultrastructural changes in the inner ear suggested that there was mitochondrial damage in response to the excessive fat intake. The expression level of cleaved caspase-3 and the number of terminal deoxynucleotidyl transferase (TdT)-mediated deoxyuridine triphosphate (dUTP) nick-end-labelling (TUNEL)-positive cells in the inner ear were increased by the HFD. The effects of D-gal on the inner ears were similar with 12 month-HFD. We found that rats receiving both the HFD and D-gal exhibited a greater shift in the ABR threshold, larger increases in the expression levels of NOX, UCP and cleaved caspase-3 and an increased number of TUNEL-positive cells in the inner ear. The present study demonstrated that HFD may induce oxidative stress, mitochondrial damage and apoptosis in the inner ear, and it provided evidence regarding the link between HFD and an increased risk of age-related hearing loss.

NADPH oxidase-dependent oxidative stress and mitochondrial damage in hippocampus of D-galactose-induced aging rats

Mitochondrial DNA (mtDNA) common deletion (CD) plays a significant role in aging and age-related diseases. In this study, we used D-galactose (D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated. Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups: D-gal group (n=10) and control group (n=10). The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay. Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus. Western blot was used to detect the protein levels of NADPH oxidase (NOX) and uncoupling protein 2 (UCP2). We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats. In comparison with the control group, the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged, and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats. This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats. These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.SummaryMitochondrial DNA (mtDNA) common deletion (CD) plays a significant role in aging and age-related diseases. In this study, we used D-galactose (D-gal) to generate an animal model of aging and the involvement and causative mechanisms of mitochondrial damage in such a model were investigated. Twenty 5-week-old male Sprague-Dawley rats were randomly divided into two groups: D-gal group (n=10) and control group (n=10). The quantity of the mtDNA CD in the hippocampus was determined using a TaqMan real-time PCR assay. Transmission electron microscopy was used to observe the mitochondrial ultrastructure in the hippocampus. Western blot was used to detect the protein levels of NADPH oxidase (NOX) and uncoupling protein 2 (UCP2). We found that the level of mtDNA CD was significantly higher in the hippocampus of D-gal-induced aging rats than in control rats. In comparison with the control group, the mitochondrial ultrastructure in the hippocampus of D-gal-treated rats was damaged, and the protein levels of NOX and UCP2 were significantly increased in the hippocampus of D-gal-induced aging rats. This study demonstrated that the levels of mtDNA CD and NOX protein expression were significantly increased in the hippocampus of D-gal-induced aging rats. These findings indicate that NOX-dependent reactive oxygen species generation may contribute to D-gal-induced mitochondrial damage.

Intratympanic injection in delayed endolymphatic hydrops

Abstract Conclusions: The present study showed that intratympanic dexamethasone injection (ITD) is a promising approach for the treatment of contralateral and ipsilateral delayed endolymphatic hydrops (DEH). Moreover, intratympanic gentamicin injection (ITG), as a chemical labyrinthectomy, is a simple alternative for controlling vertigo in patients with ipsilateral DEH. Objective: This study examined the effect of ITD or ITG on DEH. Methods: Fourteen patients with DEH completed the clinical and audio-vestibular evaluation. Among them, 10 cases (ipsilateral type: nine cases, contralateral type: one case) were treated with intratympanic injection. Four patients with ipsilateral DEH underwent ITG, five patients with ipsilateral type and one patient with contralateral type received ITD. All 10 cases were followed up for 8–48 months. Results: Complete and substantial vertigo control was achieved in four of nine ipsilateral DEH patients treated with ITG. In the other five ipsilateral cases who received ITD, two accomplished complete vertigo control and two had substantial control. In one case, the vertigo was not effectively controlled. One case of contralateral DEH underwent ITD and this case had complete vertigo control. The vertigo intensity, vertigo frequency, vertigo duration and the functional level scale after intratympanic injection was decreased significantly.

Assessment of balance and vestibular functions in patients with idiopathic sudden sensorineural hearing loss

This study investigated the relationship among the severity of hearing impairment, vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled. All of the patients underwent audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test. Significant relationship was found between vertigo and hearing loss grade (P=0.009), and between SOT VEST grade and hearing loss grade (P=0.001). The abnormal rate of oVEMP test was the highest, followed by the abnormal rates of caloric and cVEMP tests, not only in patients with vertigo but also in those without vertigo. The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo). Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010). We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo. The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo. Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs. SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients. Apart from audiometry, the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL. Better assessment of the condition will help us in clinical diagnosis, treatment and prognosis evaluation of ISSNHL.SummaryThis study investigated the relationship among the severity of hearing impairment, vestibular function and balance function in patients with idiopathic sudden sensorineural hearing loss (ISSNHL). A total of 35 ISSNHL patients (including 21 patients with vertigo) were enrolled. All of the patients underwent audiometry, sensory organization test (SOT), caloric test, cervical vestibular-evoked myogenic potential (cVEMP) test and ocular vestibular-evoked myogenic potential (oVEMP) test. Significant relationship was found between vertigo and hearing loss grade (P=0.009), and between SOT VEST grade and hearing loss grade (P=0.001). The abnormal rate of oVEMP test was the highest, followed by the abnormal rates of caloric and cVEMP tests, not only in patients with vertigo but also in those without vertigo. The vestibular end organs were more susceptible to damage in patients with vertigo (compared with patients without vertigo). Significant relationship was found between presence of vertigo and SOT VEST grade (P=0.010). We demonstrated that vestibular end organs may be impaired not only in patients with vertigo but also in patients without vertigo. The cochlear and vestibular impairment could be more serious in patients with vertigo than in those without vertigo. Vertigo does not necessarily bear a causal relationship with the impairment of the vestibular end organs. SOT VEST grade could be used to reflect the presence of vertigo state in the ISSNHL patients. Apart from audiometry, the function of peripheral vestibular end organs and balance function should be evaluated to comprehensively understand ISSNHL. Better assessment of the condition will help us in clinical diagnosis, treatment and prognosis evaluation of ISSNHL.

Modified titration intratympanic gentamicin injection for unilateral intractable Ménière’s disease

This study looked into the efficacy of a modified titration protocol of intratympanic gentamicin injection (ITG) in the patients with unilateral intractable Ménière’s disease (MD). Modified titration protocol of ITG at a low dose (20 mg/mL) was administered to 10 patients with definite unilateral intractable MD. After initial first two fixed ITGs on weekly basis, the patients might or might not be given any more injections, depending on the appearance of unilateral vestibular loss (UVL). ITG was terminated if the patients satisfied the criteria of UVL. All patients were followed-up for at least two years. The effects of ITG on the vertigo attack, functional level scores and postural balance were evaluated. Of the 10 cases, 8 showed the sign of UVL after receiving initial two ITGs and were not given any more intratympanic injections, and the other 2 patients were administered three ITGs. A two-year follow-up revealed that complete and substantial vertigo control was achieved in 9 cases, and limited vertigo control in 1 patient. Hearing level was lowered in 2 patients. The posture stability and functional level scores were improved. Our study showed that the modified titration protocol of ITG at a low dose could effectively control vertigo in patients with unilateral intractable MD.SummaryThis study looked into the efficacy of a modified titration protocol of intratympanic gentamicin injection (ITG) in the patients with unilateral intractable Ménière’s disease (MD). Modified titration protocol of ITG at a low dose (20 mg/mL) was administered to 10 patients with definite unilateral intractable MD. After initial first two fixed ITGs on weekly basis, the patients might or might not be given any more injections, depending on the appearance of unilateral vestibular loss (UVL). ITG was terminated if the patients satisfied the criteria of UVL. All patients were followed-up for at least two years. The effects of ITG on the vertigo attack, functional level scores and postural balance were evaluated. Of the 10 cases, 8 showed the sign of UVL after receiving initial two ITGs and were not given any more intratympanic injections, and the other 2 patients were administered three ITGs. A two-year follow-up revealed that complete and substantial vertigo control was achieved in 9 cases, and limited vertigo control in 1 patient. Hearing level was lowered in 2 patients. The posture stability and functional level scores were improved. Our study showed that the modified titration protocol of ITG at a low dose could effectively control vertigo in patients with unilateral intractable MD.

Sensory organization test principally reflects utricular function.

Abstract Conclusion: Our study showed that sensory organization test (SOT) could principally reflect utricular function, and our cut-score of VEST ratio (the indicator of inputs from the vestibular system in balance performance) in SOT could help to screen patients with unilateral peripheral vestibular dysfunction in non-fallers. Objectives: We aimed to know SOT reflects the function of which vestibular end organs and to assess the possibility of screening patients with peripheral vestibular dysfunction in non-fall population by means of SOT. Methods: A total of 75 patients with unilateral peripheral vestibular dysfunction underwent SOT, ocular vestibular-evoked myogenic potential (oVEMP), cervical vestibular-evoked myogenic potential (cVEMP) and caloric tests. Results: Regression model indicated that oVEMP, as an independent variable, exerted the greatest influence on VEST ratio, followed by age and cVEMP. There were no significant differences in VEST ratio among groups with different extents of peripheral vestibular involvement (p > .05). VEST ratio in the vestibular impairment groups was significantly lower than in the control group and significantly higher than in fall group (p < .01). VEST ratio in group with normal oVEMP was significantly higher than in group with abnormal oVEMP (p = .013). The cut-score between populations with functional and dysfunctional vestibule was 0.649.

Repeated courses of intratympanic dexamethasone injection are effective for intractable Meniere’s disease

Abstract Conclusion: Intra-tympanic dexamethasone injection (ITD) could serve as a first-line intra-tympanic (IT) treatment for Meniere’s disease (MD), regardless of hearing level. Even if the response to initial ITD course was unsatisfactory, a repeated course may be beneficial with some patients. Objectives: This study examined the effect of repeated courses of ITD administered on demand and investigated the possibility of ITD as an initial IT treatment for medically intractable MD patients. Method: Fifty-one patients who had been diagnosed with definite MD and given course(s) of ITD treatment were included. Vertigo control, pure tone average and functional disability scores were evaluated against the American Academy of Otolaryngology-Head and Neck Surgery guidelines for MD. Results: Vertigo disappeared or was substantially controlled in 58.8% and 23.5% of the patients, respectively, after the first ITD course. A repeated course further raised the complete vertigo control rate by 15.7% and intra-tympanic gentamycin injection could be postponed or avoided in 78.6% of the patients who required repeated IT treatment. Hearing was unchanged after the first course of ITD (p > .05). No significant differences were detected in the clinical profiles or laboratory findings between patients receiving single course of ITD and those on multiple courses (p > .05).

Intratympanic steroids injection is effective for the treatment of drop attacks with Ménière's disease and delayed endolymphatic hydrops: A retrospective study.

AbstractDrop attack (DA) associated with Ménières disease (MD) and delayed endolymphatic hydrops (DEH) is not common and may cause life-threatening clinical problems. The intratympanic dexamethasone (ITD) is one of primary treatments for MD or DEH. Our study investigated the effect of ITD on the DA associated with endolymphatic hydrops (EH).We retrospectively reviewed 10 patients with MD- and DEH-associated DA between January 2009 and December 2013 in Outpatient Department of Otolaryngology, Union Hospital, Wuhan, China. Among them, 7 patients (5 cases with MD, 2 cases of DEH) received ITD (4 times, on weekly basis). Further repeated ITD courses or intratympanic gentamicin (ITG) were given if the vertigo was not satisfactorily controlled. The number of DA and status of vertigo control after intratympanic injection were evaluated. After a follow-up study lasting from 19 to 35 months, DA in 5 cases (71.4%) disappeared after initial ITD course. In 2 cases, DA was altogether controlled after an additional intratympanic injection (repeated ITD or/and ITG).This study showed that ITD promises to be a first-line conservative treatment for MD- or DEH-related DA since the steroid possesses no inner-ear toxicity. Furthermore, for MD- or DEH-related DA refractory to ITD, ITG can be an effective alternative.

BDNF signaling in the rat cerebello‐vestibular pathway during vestibular compensation: BDNF signaling in vestibular compensation

Vestibular compensation, which is the behavioral recovery from lesions to the peripheral vestibular system, is attributed to plasticity of the central vestibular system. It has been reported that brain‐derived neurotrophic factor (BDNF) is expressed and released in an activity‐dependent manner. Upon binding to the tyrosine receptor kinase B (TrkB), BDNF can acutely modulate synaptic transmission and plasticity in the central nervous system. To assess the possible contribution of BDNF to this recovery process, we studied the expression of BDNF, TrkB.FL, TrkB.T1 and KCC2 (K+‐Cl− cotransporter isoform 2) in the bilateral medial vestibular nucleus (MVN) and the flocculus of rats at 4 h, 8 h, 1, 3 and 7 days following unilateral labyrinthectomy (UL) using immunohistochemistry, quantitative real‐time PCR and western blotting. Our results have shown that, compared with the sham controls and the contra‐lesional side, (a) the expression of BDNF and TrkB.FL increased at 4 h in the ipsi‐lesional flocculus after UL; (b) the expression of TrkB.T1 decreased at 4 h and KCC2 decreased at 8 h and 1 day in the ipsi‐lesional flocculus after UL; and (c) BDNF and TrkB.FL expression was enhanced and KCC2 expression was reduced in the ipsi‐lesional MVN at 8 h after UL. Our data supported the hypothesis that BDNF upregulation may reduce the inhibitory effects of the flocculus and commissural inhibition system by regulating inhibitory GABAergic synaptic transmission in floccular Purkinje cells and Purkinje cell terminals in the MVN. Additionally, KCC2 may be a switch in this process.

Foam pad of appropriate thickness can improve diagnostic value of foam posturography in detecting postural instability

Abstract Objective: The present study investigated the effect of foam thickness on postural stability in patients with unilateral vestibular hypofunction (UVH) during foam posturography. Methods: Static and foam posturography were performed in 33 patients (UVH group) and 30 healthy subjects (control group) with eyes open (EO) and closed (EC) on firm surface and on 1–5 foam pad(s). Sway velocity (SV) of center of pressure, standing time before falling (STBF) and falls reaction were recorded and analyzed. Results: (1) SVs had an increasing tendency in both groups as the foam pads were added under EO and EC conditions. (2) STBFs, only in UVH group with EC, decreased with foam thickness increasing. (3) Significant differences in SV were found between the control and UVH group with EO (except for standing on firm surface, on 1 and 2 foam pad(s)) and with EC (all surface conditions). (4) Receiver operating characteristic curve analysis showed that the SV could better reflect the difference in postural stability between the two groups while standing on the 4 foam pads with EC. Conclusion: Our study showed that diagnostic value of foam posturography in detecting postural instability might be enhanced by using foam pad of right thickness.