Peripheral vestibular system: Age-related vestibular loss and associated deficits

Given the interdependence of multiple factors in age-related vestibular loss (e.g., balance, vision,cognition), it is important to examine the individual contributions of these factors with ARVL. While therelationship between the vestibular and visual systems has been well studied (Bronstein et al., 2015),little is known about the association of the peripheral vestibular system with neurodegenerative disorders (Cronin et al., 2017). Further, emerging research developments implicate the vestibular system asan opportunity for examining brain function beyond balance, and into other areas, such as cognition andpsychological functioning. Additionally, the bidirectional impact of psychological functioning is understudied in ARVL. Recognition of ARVL as part of a multifaceted aging process will help guide thedevelopment of integrated interventions for patients who remain at risk for decline. In this review, wewill discuss a wide variety of characteristics of the peripheral vestibular system and ARVL, how it relatesto neurodegenerative diseases, and correlations between ARVL and balance, vision, cognitive, and psychological dysfunction. We also discuss clinical implications as well as future directions for research, withan emphasis on improving care for patients with ARVL.

Aging and the peripheral vestibular system

Whereas much has been learned about age-related auditory changes in the inner ear, relatively little is known about the aging effects on the vestibular part of the inner ear-the peripheral vestibular system. Here we review relevant literature with regard to the prevalence of vestibular dysfunction, vestibular functional and structural changes in the elderly. The prevalence of vestibular dysfunction increases with age. Functionally, as age increases, VEMP amplitudes decrease, VEMP thresholds increase, VOR gain of HIT decreases. Due to the complexity of the vestibular system, variations in subject age and measurement techniques, findings in VEMP latency and caloric tests are conflicting. To address this, a direct measure of the peripheral vestibular system should be applied. Structurally, age-related loss in vestibular ganglion and otoconia have been noted; hair cell changes are not well defined; while subcellular changes remain to be explored. Defining how the onset of vestibular dysfunction correlates with structural degeneration will offer insights into the mechanisms underlying vestibular aging.

Comparative utility of vestibular function tests in patients with peripheral and central vestibular dysfunction

Background: Bithermal caloric irrigation, video head impulse test(vHIT), and rotational testing are commonly used to assess peripheral vestibular function, but the relative clinical utility of each test in differentiating patients with peripheral vestibulopathy is debated.Objectives: To determine whether(1) the combination of two or more vestibular tests enhances diagnostic utility over a single test;(2) abnormal test results on vestibular tests correlate with one another.Methods: Retrospective analysis of data collected from multidisciplinary vestibular clinics at two academic medical centers from 2016 to 2022.Results: 150 patients(54.10 ± 15.09 years, 88 females) were included. No individual test was significantly better at predicting the presence of peripheral vestibular damage(p > 0.05). vHIT test results improved significantly when combined with either the caloric test(p = 0.007) or rotary chair test(p = 0.039). Caloric and rotational testing had high sensitivity(74.65% and 76.06%, respectively) and specificity(83.54% and 78.48%, respectively). vHIT demonstrated excellent specificity(89.87%) but poor sensitivity(47.89%). Caloric, vHIT, and rotary chair tests results did not correlate with one another(p > 0.05).Conclusions: Vestibular function tests have comparable diagnostic utility, yet each offers unique advantages. Caloric and rotational testing may be best suited for screening peripheral damage and vHIT may function ideally as a confirmatory test.

Masseter Vestibular evoked myogenic potentials: A new tool to assess the vestibulomasseteric reflex pathway

Purpose: This review article provides the readers with an in-depth insight in understanding and interpreting various research literatures on the masseter vestibular evoked myogenic potentials(mVEMP). The article also reviews the contemporary researches involving the clinical applications of the mVEMP. Conclusions: Masseter VEMP is an evolving yet clinically promising neuro-otology test tool that has recently gained more research interest and is considered an additional tool to diagnose various vestibular disorders. Masseter VEMP assesses the functional integrity of the acoustic-masseteric and vestibulo-masseteric reflex pathways. The mVEMP could be used as a complementary test to evaluate the same peripheral generator as the cervical VEMP but a different central pathway i.e., vestibulo-trigeminal pathway. Various research studies that have experimented on parameters such as the effect of different electrode montages(zygomatic vs mandibular configurations), stimulation rates, filter settings and stimuli used to evoke mVEMP have been discussed in this article that could assist in the optimization of a comprehensive clinical protocol. The latency and the amplitude of mVEMP waveforms serve as significant parameters in differentiating normals from those of the clinical populations. Along with the cVEMPs and oVEMPs, mVEMP might help diagnose brainstem lesions in REM Sleep behaviour disorders, Multiple Sclerosis and Parkinson's disease. However, further studies are required to probe in this area of research.

Effect of health education based on information-motivationbehavioral skills model on patients with unilateral vestibular dysfunction

BACKGROUND Vestibular dysfunction(VH)is a common concomitant symptom of late peri-pheral vestibular lesions,which can be trauma,poisoning,infection,heredity,and neurodegeneration,but about 50%of the causes are unknown.The study uses the information-motivation-behavioral skills(IMB)model for health education,effectively improve the quality of life,increase their self-confidence,reduce anxiety and depression,and effectively improve the psychological state of patients.AIM To explore the effect of health education based on the IMB model on the degree of vertigo,disability,anxiety and depression in patients with unilateral vestibular hypofunction.METHODS The clinical data of 80 patients with unilateral vestibular hypofunction from January 2019 to December 2021 were selected as the retrospective research objects,and they were divided into the control group and the observation group with 40 cases in each group according to different nursing methods.Among them,the control group was given routine nursing health education and guidance,and the observation group was given health education and guidance based on the IMB model.The changes in self-efficacy,anxiety and depression,and quality of life of patients with unilateral VH were compared between the two groups.RESULTS There was no significant difference in General Self-Efficacy Scale(GSES)scale scores between the two groups of patients before nursing(P>0.05),which was comparable;after nursing,the GSES scale scores of the two groups were higher than those before nursing.The nursing group was higher than the control group,and the difference was statistically significant(P<0.05).There was no significant difference in the scores of Hospital Anxiety and Depression Scale(HADS)and anxiety and depression subscales between the two groups before nursing(P>0.05).After nursing,the HADS score,anxiety,and depression subscale scores of the two groups of patients were lower than those before nursing,and the nursing group was lower than the control group,and the difference was statistically significant(P<0.05).After nursing,the Dizziness Handicap Inventory(DHI)scale and DHI-P,DHI-E and DHI-F scores in the two groups were decreased,and the scores in the nursing group were lower than those in the control group,and the difference was statistically significant(P<0.05).CONCLUSION Health education based on the IMB model can effectively improve patients'quality of life,increase self-efficacy of patients with unilateral vestibular hypofunction,enhance patients'confidence,enable patients to resume normal work and life as soon as possible,reduce patients'anxiety and depression,and effectively improve patients'psychological status.

Saccades of video head impulse test in Meniere's disease and Vestibular Migraine: What can we learn from?

Background:Saccades are often observed on video head impulse tests(vHIT)in patients with Meniere's Disease(MD)and Vestibular Migraine(VM).However,their saccadic features are not fully described.Objective:This study aims to identify the saccades characteristics of MD and VM.Methods:75 VM patients and 103 definite unilateral MD patients were enrolled in this study.First raw saccades were exported and analyzed.The VM patients were divided into left and right based on their ears,while the MD patients were separated into affected and unaffected subgroups based on their audiograms and symptoms.Results:The MD patients have more saccades on the affected side(85%vs.69%),and saccade velocity is more consistent than the contralateral side(shown by the coefficient of variation).The saccades occurrence rates on both sides are similar in VM(77%vs.76%),as are other saccadic parameters.The MD patients have more significant inter-aural differences than the VM patients,manifested in higher velocity(p-value 0.000),earlier arriving(p-value 0.010),and more time-domain gathered(p-value 0.003)on the affected side.Conclusions:Bilateral saccades are commonly observed in MD and VM.In contrast to MD,saccades on VM are subtle,scattered,and late-arrived.Furthermore,the MD patients showed inconsistent saccadic distribution with more velocity-uniform saccades on the affected side.

Innervation of Cholinergic Vestibular Efferent System in Vestibular Periphery of Rats

The innervation of cholinergic efferent fibers in the vestibular endorgans of the rat was investigated using a modified preembedding immunostaining technique of immunoelectron microscopy. A monoclonal antibody to choline acetyltransferase (ChAT) was used as a marker of cholinergic fibers. It was found that there were four types of cholinergic innervation in the vestibular endorgans of the rat: (1) cholinergic nerve endings formed axo-dendritic synapses with afferent chalice surrounding the type I sensory hair cells; (2) cholinergic nerve endings formed axo-somatic synapses with type Ⅱ hair cells; (3) cholinergic fibers synapse with afferent nerve fibers and (4) a synaptic contact developed between cholinergic nerve endings. The results demonstrated that a multiform innervation of the cholinergic efferents exists in the rat vestibular periphery.

Vestibular migraine in low-and lower-middle-income countries:A scoping review

Background:Vestibular migraine(VM)is a common cause of dizziness that is underrecognized,underdiagnosed,and challenging to effectively treat.The prevalence,appropriate diagnostic workup,and therapies for VM in low-and lower-middle-income countries(LLMICs)remain understudied.The objective of this scoping review is to evaluate the current state of VM research in LLMICs.Methods:PubMed,Embase,and Web of Science databases were searched to execute a scoping review of VM.Keywords“vestibular diseases”and“vertigo”were used in combination with terms referring to LLMICs as defined by the World Bank.Title and abstract screening,full-text review,and data collection were conducted by two authors independently.Results:Twenty-six studies were included in the scoping review.Most studies were cross-sectional(57.7%)or case studies/series(23.1%)and were conducted in urban settings only(92.3%).Geographic distribution of studies was skewed,with 65.4%of articles originating from India.The prevalence of VM among clinic patients ranged from 0.3%to 33.3%.VM most frequently presented as headache,nausea and vomiting,and photophobia.Radiographic imaging,audiometry,and electronystagmography/videonystagmography were the three most commonly utilized diagnostic modalities in the dizziness workup.The most studied pharmacotherapies included calcium channel blockers,followed by beta-blockers and antiepileptics.Case studies and series discussed less common VM pharmacotherapies,such as ayurvedic medicine.Conclusions:There is a need for more VM research in LLMICs,including innovative diagnostic approaches and therapies that can improve VM care globally.Equitable partnerships between LLMIC and highincome country researchers must expand vestibular research capacity and productivity in LLMICs.

Vestibular rehabilitation in cerebellar ataxia with neuropathy and vestibular areflexia syndrome(CANVAS)-A case report

Background and purpose:Cerebellar ataxia,neuropathy,and vestibular areflexia syndrome(CANVAS)is a neurodegenerative disease of the cerebellum.The disease progression is slow,with up to 25%of people diagnosed needing to use a wheelchair after 15 years from diagnosis.Vestibular symptoms arise from centrally-mediated ocular movement degradation and the reduced vestibular-ocular reflex functioning bilaterally.To date,no report has shown an improvement in VOR gain or gait outcome measures in someone with CANVAS after a course of vestibular physical therapy.Case description:A 65-year-old male,Patient X,first noticed symptoms in his fourth decade of life and was diagnosed with(CANVAS)in his seventh decade.Patient X reported numbness and tingling in his hands and feet,decreased ability to perform daily activities,and several falls.Intervention:Patient X completed a four-month course of vestibular physical therapy,including vestibular ocular reflex exercises,balance training,gait training,and the VestAid application for eye gaze compliance monitoring.The Vestaid application uses eyes and facial recognition software to record the percentage of time that the patient kept their eyes on the target.Outcomes:After vestibular therapy,Patient X had a clinically meaningful improvement in gait speed:from 1.02 m/s to 1.13 m/s and in the Functional Gait Assessment from 20/30 to 27/30.Patient X's eye gaze compliance improved from a median of 43%(range 25e68%)to a median of 67%(58e83%).Discussion:This case study demonstrates that vestibular rehabilitation improved eye gaze compliance and functional outcomes in a person living with CANVAS.

The minimal clinically important difference for gait speed in significant unilateral vestibular hypofunction after vestibular rehabilitation

Gait speed is a valid measure of both physical function and vestibular health.Vestibular rehabilitation is useful to improve gait speed for patients with vestibular hypofunction,yet there is little data to indicate how changes in gait speed reflect changes in patient-reported health outcomes.We determined the minimal clinically important difference in the gait speed of patients with unilateral vestibular hypofunction,mostly due to deafferentation surgery,as anchored to the Dizziness Handicap Index and the Activities Balance Confidence scale,validated using regression analysis,change difference,receiveroperator characteristic curve,and average change methods.After six weeks of vestibular rehabilitation,a change in gait speed from 0.20 to 0.34 m/s with 95%confidence was required for the patients to perceive a significant reduction in perception of dizziness and improved balance confidence.

Misdiagnosis of Facial Nerve Palsy: A Case Report of Sporadic Vestibular Schwannomas (Non-NFM2) Causing Facial Nerve Palsy Be Misled by Bell’s Palsy in a Child

We report a case of a rare sporadic Vestibular Schwannoma of a 9-month-old girl who had a right-sided lower motor type facial nerve palsy. The patient was initially diagnosed with Bell’s palsy and received steroid treatment accordingly, two months later the patient’s condition deteriorated, and further evaluation of CT and MRI brain was conducted that showed a mass lesion in the posterior fossa causing compression on the facial nerve. Misdiagnosis of facial nerve paralysis is common among children due to multiple related etiologies and varying rates of incidence in comparison to adults. The authors hope to address this issue in this report. Background: Facial nerve paralysis has been a matter of concern for many researchers to understand its nature, causes and presentation according to different age groups. In adults, Bell’s palsy (BP), the idiopathic form of facial nerve paralysis, is more common compared to children where most cases are due to secondary etiologies. Therefore, pediatricians are in an important position to identify these patients early in order to launch the most effective diagnostic and treatment approaches.

Non-Traditional Management of Vestibular Migraine (Review)

Objectives: Vestibular migraine is one of the most common causes of episodic vertigo in adults and even in children. Traditional;management may have a side effect on the long run. So the aim of this review is to explain the other non-medical lines of management for patients with migraine. Methods: English articles from Medline and Cochrane library were searched and reviewed. Results: Evidence indicates that non-traditional management has a prophylactic and therapeutic effect on migraine patients with all its steps. Conclusion: Due to the possible side effects of pharmacological drugs and drug addictions, the use of non-traditional management alone or in combination with normal cures have been proposed. However, further constructive studies are required.

Modification of tenascin-R expression following unilateral labyrinthectomy in rats indicates its possible role in neural plasticity of the vestibular neural circuit

We have previously found that unilateral labyrinthectomy is accompanied by modification of hyaluronan and chondroitin sulfate proteoglycan staining in the lateral vestibular nucleus of rats and the time course of subsequent reorganization of extracellular matrix assembly correlates to the restoration of impaired vestibular function. The tenascin-R has repelling effect on pathfinding during axonal growth/regrowth, and thus inhibits neural circuit repair. By using immunohistochemical method, we studied the modification of tenascin-R expression in the superior, medial, lateral, and descending vestibular nuclei of the rat following unilateral labyrin- thectomy. On postoperative day 1, tenascin-R reaction in the perineuronal nets disappeared on the side of labyrinthectomy in the superior, lateral, medial, and rostral part of the descending vestibular nuclei. On survival day 3, the staining intensity of tenascin-R reaction in perineuronal nets recovered on the operated side of the medial vestibular nucleus, whereas it was restored by the time of postoperative day 7 in the superior, lateral and rostral part of the descending vestib- ular nuclei. The staining intensity of tenascin-R reaction remained unchanged in the caudal part of the descending vestibular nucleus bilaterally. Regional differences in the modification of tena- scin-R expression presented here may be associated with different roles of individual vestibular nuclei in the compensatory processes. The decreased expression of the tenascin-R may suggest the extracellular facilitation of plastic modifications in the vestibular neural circuit after lesion of the labyrinthine receptors.

Multisensory mechanisms of gait and balance in Parkinson’s disease:an integrative review

Understanding the neural underpinning of human gait and balance is one of the most pertinent challenges for 21st-century translational neuroscience due to the profound impact that falls and mobility disturbances have on our aging population.Posture and gait control does not happen automatically,as previously believed,but rather requires continuous involvement of central nervous mechanisms.To effectively exert control over the body,the brain must integrate multiple streams of sensory information,including visual,vestibular,and somatosensory signals.The mechanisms which underpin the integration of these multisensory signals are the principal topic of the present work.Existing multisensory integration theories focus on how failure of cognitive processes thought to be involved in multisensory integration leads to falls in older adults.Insufficient emphasis,however,has been placed on specific contributions of individual sensory modalities to multisensory integration processes and cross-modal interactions that occur between the sensory modalities in relation to gait and balance.In the present work,we review the contributions of somatosensory,visual,and vestibular modalities,along with their multisensory intersections to gait and balance in older adults and patients with Parkinson’s disease.We also review evidence of vestibular contributions to multisensory temporal binding windows,previously shown to be highly pertinent to fall risk in older adults.Lastly,we relate multisensory vestibular mechanisms to potential neural substrates,both at the level of neurobiology(concerning positron emission tomography imaging)and at the level of electrophysiology(concerning electroencephalography).We hope that this integrative review,drawing influence across multiple subdisciplines of neuroscience,paves the way for novel research directions and therapeutic neuromodulatory approaches,to improve the lives of older adults and patients with neurodegenerative diseases.

Effect of rotary motion on Fos protein expression in the vestibular-related nucleus population in a mouse model of rapid retinal degeneration

BACKGROUND： Previous studies on integration mechanisms of visual and vestibular information in the central nervous system have focused on the vestibular system. Due to the lack of an appropriate animal model, few studies have addressed the visual system with regard to visual and vestibular information. OBJECTIVE： To investigate Fos protein expression differences of vestibular-related nucleus populations in a mouse model of rapid retinal degeneration and normal wild-type Kunming mice following rotary motion, and to verify integration regions of visual and vestibular information in the central nervous system. DESIGN, TIME AND SETTING： A randomized, controlled in vitro study was performed at the Key Laboratory of Aerospace Medicine of Ministry of Education, China from March 2008 to February 2009. MATERIALS： A rotary stimulation device was re-fit to an electric, rotating chair produced by the School of Aerospace Medicine, the Fourth Military Medical University. METHODS： A total of 12 rapid retinal degeneration mice and 12 normal wild-type male Kunming mice were randomly assigned to experimental and control subgroups, respectively （n = 6）. Mice in the experimental group were exposed to rotary motion at a speed of 180°/s, 3 minutes per cycle, in an alternating clockwise/counterclockwise movement. Mice in the control group were not exposed to rotary motion. MAIN OUTCOME MEASURES： Differences in the number of Fos-positive neurons were determined in the vestibular nucleus, prepositus hypoglossal nucleus, inferior olive subnucleus beta, Kooy cap of the inferior olive medial nucleus, and the flocculus and paraflocculus of the cerebellum in rapid retinal degeneration mice and normal wild-type Kunming mice. RESULTS： The number of Fos-positive neurons was reduced in the prepositus hypoglossal nucleus and the Kooy cap of the inferior olive medial nucleus in the rapid retinal degeneration mice following 30 minutes of rotary motion in the experimental group, compared with the normal wild-type Kunming mice （P 〈 0.01）. There was no significant difference in Fos protein expression in the vestibular nucleus, inferior olive subnucleus beta, and the flocculus and paraflocculus of the cerebellum between the rapid retinal degeneration mice and normal wild-type Kunming mice. CONCLUSION： Visual information affected neuronal activation in the prepositus hypoglossal nucleus and the Kooy cap of the inferior olive medial nucleus in mice following rotary motion. The prepositus hypoglossal nucleus and the dorsal cap of Kooy of inferior olive medial nucleus were shown to be key integration regions of visual information and vestibular information in the central nervous system.

Lesion-induced changes of brevican expression in the perineuronal net of the superior vestibular nucleus

Damage to the vestibular sense organs evokes static and dynamic deficits in the eye movements,posture and vegetative functions.After a shorter or longer period of time,the vestibular function is partially or completely restored via a series of processes such as modification in the efficacy of synaptic inputs.As the plasticity of adult central nervous system is associated with the alteration of extracellular matrix,including its condensed form,the perineuronal net,we studied the changes of brevican expression in the perineuronal nets of the superior vestibular nucleus after unilateral labyrinth lesion.Our results demonstrated that the unilateral labyrinth lesion and subsequent compensation are accompanied by the changing of brevican staining pattern in the perineuronal nets of superior vestibular nucleus of the rat.The reduction of brevican in the perineuronal nets of superior vestibular nucleus may contribute to the vestibular plasticity by suspending the non-permissive role of brevican in the restoration of perineuronal net assembly.After a transitory decrease,the brevican expression restored to the control level parallel to the partial restoration of impaired vestibular function.The bilateral changing in the brevican expression supports the involvement of commissural vestibular fibers in the vestibular compensation.All experimental procedures were approved by the 'University of Debrecen–Committee of Animal Welfare'(approval No.6/2017/DEMAB) and the 'Scientific Ethics Committee of Animal Experimentation'(approval No.HB/06/éLB/2270-10/2017;approved on June 6,2017).

Vestibular Function Evaluation in Endemic Diseases Combat Agents

Introduction: Simultaneous exposure to certain chemical agents and noise may cause synergistic, additive or potentiating effects on the auditory and vestibular system. However, there is still a lack of studies investigating simultaneous exposure to pesticides and noise in the vestibular system. Purpose: To analyze the findings of the vestibular evaluation of endemic diseases combat agents when simultaneously exposed to pesticides and noise. Method: Thirty-three male pesticide-exposed and noise-fighting endemic diseases combat agents participated in the study. The age range was 48 to 67 years (mean = 56 years). All participants underwent vestibular examinations, such as positional nystagmus research, spontaneous nystagmus with open and closed eyes, semi-spontaneous nystagmus, optokinetic nystagmus, pendular screening, per rotatory, caloric tests and tonal audiometry. Data were analyzed by descriptive statistics. Results: Altered exams were presented in 36.4% of the cases. There was no statistically significant relationship between pesticide handling time and test results (p = 0.2825). The results of pure tone audiometry correlated significantly (p = 0.0494) with the vestibular exams, as participants who presented with worse hearing thresholds at the frequency of 4000 Hz in the right ear also presented altered results in the vestibular exam. Conclusion: The present study concluded that more than 1/3 of the studied population presented with vestibular dysfunction, which was related to anterior and posterior labyrinth alteration (Cochlear-Vestibular Syndrome). No central vestibular alteration was noted in this population.

“Wait and scan” management of patients with vestibular schwannoma and the relevance of non-contrast MRI in the follow-up

Vestibular schwannoma(VS) is a slow-growing benign neoplasm. There has been an evolution in the management of VS from active treatments(microsurgery and stereotactic radiotherapy) to conservative management(wait and scan). Regular MRI scanning is necessary to monitor tumor progression. Conservative management causes significantly less complications and offers a higher quality of life compared with active treatments. The mean growth rate of VS varies from 0.4 to 2.9 mm/year, and spontaneous shrinkage is observed in 3.8 percent of tumors during observation. If significant growth occurs, active treatment is considered. Significant growth is defined as an increase of at least 3 mm in the largest extrameatal diameter in any plane between the first and last available scans. The vestibulocochlear nerve is surrounded by cerebrospinal fluid, which provides natural contrast for MRI; thus, gadolinium may not be needed to detect VS. Specific sequences have high sensitivity, specificity, and accuracy for detection of progression. Hypointense signal in the ipsilateral inner ear fluid might be a useful sign to distinguish VS from meningioma. In this paper, we summarize the current status of research on conservative management and non-contrast MRI for the detection of VS.

Investigation of the usefulness of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function

Background:Military operation personnel often suffer from sleep difficulty because of their work requirements.In this study,we investigated the efficacy of zaleplon at two doses to induce afternoon-sleep under noise interference and its effects on psychomotor performance and vestibular function; we subsequently established the optimal dosage regimen for military operation personnel.Methods:Twenty-two healthy young male volunteers were recruited for the study.Eight subjects took 10 mg or 15 mg of zaleplon and placebo alternately and then were exposed to noise.Changes in polysomnography(PSG) indices,including sleep latency(SL),sleep efficiency(SE) and sleep structure,were recorded after drug administration.After awakening,the volunteers' subjective judgments of sleep quality and sleepiness were measured.Eight volunteers underwent 3 psychomotor performance tests at a one-week interval,and the psychomotor performance tests were conducted before and after taking zaleplon and placebo.Six volunteers participated in the vestibular function test session,and parameters,including optokinetic nystagmus(OKN),vestibular ocular reflex(VOR),visualvestibular ocular reflex(VVOR) and vestibular ocular reflex fixation suppression(VOR-Fix),were detected by the same experimental design as described above.The data of sleep observations were subjected to one-way variance analysis.Results:Compared with the placebo group,SL was shortened significantly,and the scores of subjective sleep quality and sleep depth were clearly increased in the zaleplon 10 mg group(P<0.05).Moreover,the SE and the percent of REM(rapid eye movement) sleep were increased remarkably in the zaleplon 15 mg group(P<0.01).Furthermore,the SE,percent of REM sleep and scores of subjective sleep depth in the zaleplon 15 mg group were significantly higher than in the zaleplon 10 mg group(P<0.05).The psychomotor performance did not change significantly after ingestion of 10 mg or 15 mg of zaleplon,whereas the OKN and VOR gains were lower in the two dose groups of zaleplon(P<0.05) and restored to normal 3h after drug ingestion.Conclusion:Zaleplon is an ideal hypnotic for military personnel,and its hypnotic efficiency is dose-related under noise interference; a 15 mg dose of zaleplon could provide significantly better sleep than a 10 mg dose of zaleplon.

Cisplatin-induced vestibular hair cell lesion-less damage at high doses

Cisplatin, a widely used anticancer drug, damages hair cells in cochlear organotypic cultures at low doses, but paradoxically causes little damage at high doses resulting in a U-shaped dose-response function. To determine if the cisplatin dose-response function for vestibular hair cells follows a similar pattern, we treated vestibular organotypic cultures with doses of cisplatin ranging from 10 to 1000 μM. Vestibular hair cell lesions progressively increased as the dose of cisplatin increased with maximum damage occurring around 50-100 μM, but the lesions progressively decreased at higher doses resulting in little hair cell loss at 1000 μM. The U-shaped doseresponse function for cisplatin-treated vestibular hair cells in culture appears to be regulated by copper transporters, Ctrl, ATP7A and ATP7B, that dose-dependently regulate the uptake, sequestration and extrusion of cisplatin.