An Evaluation of the Vestibular System in Individuals Aged 40-65 Years with Sensorineural Hearing Loss.

Objectives: Vestibular dysfunction occasionally accompanies sensorineural hearing loss (SNHL) due to anatomical proximity of cochlea and vestibule. The aim of the present study was to evaluate the vestibular system objectively and subjectively in 40-to 65-year-old individuals with and without SNHL. Methods: This study included participants of both sexes, between the ages of 40 and 65 years old. There were 31 participants with SNHL and 31 control participants. First of all, participants were grouped in the control and SNHL groups based on the results of their hearing test, which included audiometry and immitance evaluation. Subsequently, for vestibular evaluation, each participant was evaluated subjective with "Dizziness Handicap Inventory" (DHI) as well as with objective tests battery that included positional tests with videonystagmogrophy (VNG) and vestibuloocular reflex (VOR) assessment using the vestibular head impulse test (vHIT). Results: Peripheral nystagmus was found to be significantly higher in patients with SNHL based on the head shake and positional tests (p<0.05). There was a positive correlation between DHI scores and positional test findings of the participants with SNHL (p<0.05). When the VHIT VOR gain values were compared between groups, there was no significant difference (p<0.05). Conclusion: In our study, vestibular involvement was frequently observed in 40- to 65-year-old individuals with SNHL. Therefore, vestibular evaluation should be considered along with the assessment of hearing in individuals with SNHL who are over 40 years old.

Human senses and sensors from Aristotle to the present.

This historical review on the semantic evolution of human senses and sensors revealed that Aristotle's list of the five senses sight, hearing, touch, taste, and smell is still in use among non-scientific lay persons. It is no surprise that his classification in the work "De Anima" (On the Soul) from 350 BC confuses the sensor "touch" with the now more comprehensively defined somatosensory system and that senses are missing such as the later discovered vestibular system and the musculotendinous proprioception of the position of parts of the body in space. However, it is surprising that in the three most influential ancient cultures, Egypt, Greece, and China-which shaped the history of civilization-the concept prevailed that the heart rather than the brain processes perception, cognition, and emotions. This "cardiocentric view" can be traced back to the "Doctrine of Aristotle," the "Book of the Dead" in ancient Egypt, and the traditional Chinese medicine of correspondence documented in the book "Huang di Neijing." In Greek antiquity the philosophers Empedocles, Democritus and Aristotle were proponents of the allocation of the spirit and the soul to the heart connected to the body via the blood vessels. Opponents were the pre-Socratic mathematician Pythagoras, the philosopher Plato, and especially the Greek physician Hippocrates who regarded the brain as the most powerful organ in humans in his work "De Morbo Sacro." The Greek physician Galen of Pergamon further elaborated on the concept of the brain ("cephalocentric hypothesis") connected to the body by a network of nerves. The fundamental concepts for understanding functions and disorders of the vestibular system, the perception of self-motion, verticality and balance control were laid by a remarkable group of 19th century scientists including Purkynӗ, Mach, Breuer, Helmholtz, and Crum-Brown. It was also in the 19th century that Bell described a new sense of a reciprocal sensorimotor loop between the brain and the muscles which he called "muscular sense," later termed "kinaesthesia" by Bastian and defined in 1906 as "proprioception" by Sherrington as "the perception of joint and body movements as well as position of the body or body segments, in space." Both, the vestibular system and proprioception could be acknowledged as senses six or seven. However, we hesitate to recommend "pain"-which is variously assigned to the somatosensory system or extero-, intero-, visceroception-as a separate sensory system. Pain sensors are often not specific but have multisensory functions. Because of this inconsistent, partly contradictory classification even by experts in the current literature on senses and sensors we consider it justified to recommend a comprehensive reorganization of classification features according to the present state of knowledge with an expansion of the number of senses. Such a project has also to include the frequent task-dependent multisensory interactions for perceptual and sensorimotor achievements, and higher functions or disorders of the visual and vestibular systems as soon as cognition or emotions come into play. This requires a cooperation of sensory physiologists, neuroscientists and experienced physicians involved in the management of patients with sensory and multisensory disorders.

Vestibular Rehabilitation Using Dynamic Posturography: Objective and Patient-Reported Outcomes from a Randomized Trial.

OBJECTIVE: Balance deficits are common and debilitating. Standard treatments have limitations in addressing symptoms and restoring dynamic balance function. This study compares a rehabilitative computerized dynamic posturography (CDP) protocol, computerized vestibular retraining therapy (CVRT), with a home exercise program (HEP) for patients with objectively confirmed unilateral vestibular deficits (UVDs). STUDY DESIGN: Single-center, randomized, interventional trial, with 1-sided crossover. SETTING: A tertiary neurotology clinic. METHODS: Patients with UVDs and Dizziness Handicap Inventory (DHI) score >30 were randomized to receive either CVRT or HEP. After completion of treatment, the HEP group was crossed over to CVRT. Outcome measures were the sensory organization test (SOT) and 3 participants reported dizziness disability measures: the DHI, Activity-Specific Balance Confidence Scale (ABC) scale, and Falls Efficacy Score-International (FES-I). RESULTS: We enrolled 37 patients: 18 participants completed CVRT and 12 completed HEP, 11 of whom completed the crossover. Seven participants withdrew. The CVRT group demonstrated a greater improvement in SOT composite score than the HEP group (P = .04). Both groups demonstrated improvement in participant-reported measures but there were no differences between groups (DHI: P = .2604; ABC: P = .3627; FES-I: P = .96). Following crossover to CVRT after HEP, SOT composite (P = .002), DHI (P = .03), and ABC (P = .006) improved compared to HEP alone. CONCLUSION: CVRT and HEP were both associated with improved participant-reported disability outcomes. CVRT was associated with greater improvement in objective balance than HEP. Adding CVRT after HEP was superior to HEP alone. Multimodal CDP-based interventions, such as CVRT, should be considered as an adjunct to vestibular physiotherapy for patients with UVD.

Vestibular dysfunction in Parkinson's disease: a neglected topic.

Dizziness and postural instability are frequently observed symptoms in patient with Parkinson's disease (PD), potentially linked to vestibular dysfunction. Despite their significant impact on quality of life, these symptoms are often overlooked and undertreated in clinical practice. This review aims to summarize symptoms associated with vestibular dysfunction in patients with PD and discusses vestibular-targeted therapies for managing non-specific dizziness and related symptoms. We conducted searches in PubMed and Web of Science using keywords related to vestibular dysfunction, Parkinson's disease, dizziness, and postural instability, alongside the reference lists of relevant articles. The available evidence suggests the prevalence of vestibular dysfunction-related symptoms in patients with PD and supports the idea that vestibular-targeted therapies may be effective in improving PD symptoms.

Impact of repetitive home-based galvanic vestibular stimulation on cognitive skills in healthy older adults.

The human vestibular system is adversely affected by the aging process. Recent evidence indicates that vestibular information and cognitive functions are related, suggesting that age-related vestibular loss may contribute to cognitive impairment. In this study, we aimed to investigate the effects of repetitive, home-based galvanic vestibular stimulation (GVS) on cognitive functions in healthy older adults. Twenty-one participants (age = 64.66 ± 2.97 years, 12 females) were randomly allocated to either a home-based GVS or an active control group. The GVS intervention lasted 20 min per session, five times a week, for two weeks (10 sessions). Cognitive functions were assessed before and after the intervention using the Stroop Test, Trail Making Test A&B, and Dual-Task (digit recall and paper-pencil tracking test). Our findings revealed a significant group-by-time interaction effect for the tracking accuracy (F(1,18) = 7.713, p = 0.012, η p2 = 0.30), with only the home-based GVS group showing significant improvement (t = -2.544, p = 0.029). The proposed home-based GVS protocol offers a promising non-pharmacological avenue for enhancing visuospatial ability in healthy older adults. Further research is needed to investigate the effects of different GVS protocols on various cognitive functions, particularly in older individuals with different health conditions.

Head movements induced by voluntary neck flexion stabilize sensorimotor synchronization of the finger to syncopated auditory rhythms.

Head movements that are synchronized with musical rhythms often emerge during musical activities, such as hip hop dance. Although such movements are known to affect the meter and pulse perception of complex auditory rhythms, no studies have investigated their contribution to the performance of sensorimotor synchronization (SMS). In the present study, participants listened to syncopated auditory rhythms and flexed their dominant hand index finger in time with the perceived pulses (4/4 meters). In the first experiment (Exp. 1), the participants moved their heads via voluntary neck flexion to the pulses in parallel with finger SMS (Nodding condition, ND). This performance was compared with finger SMS without nodding (Without Nodding condition, WN). In the second experiment (Exp. 2), we investigated the specificity of the effect of head SMS on finger SMS confirmed in Exp. 1 by asking participants to flex their bilateral index fingers to the pulses (Bimanual condition, BM). We compared the performance of dominant hand finger SMS between the BM and ND conditions. In Exp. 1, we found that dominant hand finger SMS was significantly more stable (smaller standard deviation of asynchrony) in the ND versus WN condition (p < 0.001). In Exp. 2, dominant hand finger SMS was significantly more accurate (smaller absolute value of asynchrony) in the ND versus BM condition (p = 0.037). In addition, the stability of dominant hand finger SMS was significantly correlated with the index of phase locking between the pulses and head SMS across participants in the ND condition (r = -0.85, p < 0.001). In contrast, the stability of dominant hand finger SMS was not significantly correlated with the index of phase locking between pulses and non-dominant hand finger SMS in the BM condition (r = -0.25, p = 0.86 after multiple comparison correction). These findings suggest that SMS modulation depends on the motor effectors simultaneously involved in synchronization: simultaneous head SMS stabilizes the timing of dominant hand finger SMS, while simultaneous non-dominant hand finger SMS deteriorates the timing accuracy of dominant hand finger SMS. The present study emphasizes the unique and crucial role of head movements in rhythmic behavior.

Non-additive effects of electrical stimulation of the dorsolateral prefrontal cortex and the vestibular system on muscle sympathetic nerve activity in humans.

Sinusoidal galvanic vestibular stimulation (sGVS) induces robust modulation of muscle sympathetic nerve activity (MSNA) alongside perceptions of side-to-side movement, sometimes with an accompanying feeling of nausea. We recently showed that transcranial alternating current stimulation (tACS) of the dorsolateral prefrontal cortex (dlPFC) also modulates MSNA, but does not generate any perceptions. Here, we tested the hypothesis that when the two stimuli are given concurrently, the modulation of MSNA would be additive. MSNA was recorded from 11 awake participants via a tungsten microelectrode inserted percutaneously into the right common peroneal nerve at the fibular head. Sinusoidal stimuli (± 2 mA, 0.08 Hz, 100 cycles) were applied in randomised order as follows: (i) tACS of the dlPFC at electroencephalogram (EEG) site F4 and referenced to the nasion; (ii) bilateral sGVS applied to the vestibular apparatuses via the mastoid processes; and (iii) tACS and sGVS together. Previously obtained data from 12 participants supplemented the data for stimulation protocols (i) and (ii). Cross-correlation analysis revealed that each stimulation protocol caused significant modulation of MSNA (modulation index (paired data): 35.2 ± 19.4% for sGVS; 27.8 ± 15.2% for tACS), but there were no additive effects when tACS and sGVS were delivered concurrently (32.1 ± 18.5%). This implies that the vestibulosympathetic reflexes are attenuated with concurrent dlPFC stimulation. These results suggest that the dlPFC is capable of blocking the processing of vestibular inputs through the brainstem and, hence, the generation of vestibulosympathetic reflexes.

Comparative biology of the amniote vestibular utricle.

The sensory epithelia of the auditory and vestibular systems of vertebrates have shared developmental and evolutionary histories. However, while the auditory epithelia show great variation across vertebrates, the vestibular sensory epithelia appear seemingly more conserved. An exploration of the current knowledge of the comparative biology of the amniote utricle, a vestibular sensory epithelium that senses linear acceleration, shows interesting instances of variability between birds and mammals. The distribution of sensory hair cell types, the position of the line of hair bundle polarity reversal and the properties of supporting cells show marked differences, likely impacting vestibular function and hair cell regeneration potential.

Development of a ground-based sensorimotor disorientation analog to replicate astronaut postflight experience.

The perceptual and motor coordination problems experienced following return from spaceflight reflect the sensory adaptation to altered gravity. The purpose of this study was to develop a ground-based analog that replicates similar sensorimotor impairment using a standard measures test battery and subjective feedback from experienced crewmembers. This Sensorimotor Disorientation Analog (SDA) included varying levels of sensorimotor disorientation through combined vestibular, visual, and proprioceptive disruptions. The SDA was evaluated on five previously flown astronauts to compare with their postflight experience and functional motor performance immediately (Return (R)+0 days) and +24 h (R+1) after landing. The SDA consisted of galvanic vestibular stimulation (GVS), visual disruption goggles, and a weighted suit to alter proprioceptive feedback and replicate perceived heaviness postflight. Astronauts reported that GVS alone replicated ∼50-90% of their postflight performance with the weighted suit fine-tuning the experience to replicate an additional 10%-40% of their experience. Astronauts did not report feeling that the disruption goggles represented either the visual disruptions or illusory sensations that they experienced, nor did they impact motor performance in postflight tasks similarly. Based on these results, we recommend an SDA including the GVS and the weighted suit. These results provide a more realistic and portable SDA framework to provide transient spaceflight-relevant sensorimotor disruptions for use in countermeasure testing and as a pre-flight training tool.

Video head impulse test in subacute and chronic stroke survivors: new perspectives for implementation of assessment in rehabilitation.

INTRODUCTION: The Video Head Impulse Test (vHIT) is a safe and reliable assessment of peripheral vestibular function. Many studies tested its accuracy in clinical settings for differential diagnosis and quantification of the vestibulo-oculomotor reflex (VOR) in various disorders. However, the results of its application after lesions of the CNS are discordant and have never been studied in rehabilitation. This study aims to assess the VOR performance in a sample of stroke survivors. METHODS: This is a cross-sectional study on 36 subacute and chronic stroke survivors; only persons with first-ever stroke and able to walk independently, even with supervision, were included. We performed VOR assessments for each semicircular canal by vHIT and balance assessments by the Berg Balance Scale and the MiniBESTest scale. RESULTS: Two hundred and sixteen semicircular canals were assessed using the Head Impulse paradigm (in both the vertical and horizontal planes), while 72 semicircular canals were assessed using the Suppressed Head Impulse paradigm (horizontal plane). There was a high prevalence of participants with dysfunctional canals, particularly for the left anterior and right posterior canals, which were each prevalent in more than one-third of our sample. Furthermore, 16 persons showed an isolated canal dysfunction. The mean VOR gain for the vertical canals had confidence intervals out of the normal values (0.74-0.91 right anterior; 0.74-0.82 right posterior; 0.73-0.87 left anterior). CONCLUSION: Our findings suggest that peripheral vestibular function may be impaired in people with stroke; a systematic assessment in a rehabilitation setting could allow a more personalized and patient-centred approach.

Evaluation of Balance with Computerized Dynamic Posturography in Children with Otitis Media.

BACKGROUND: Otitis media with effusion (OME) frequently leads to vestibular symptoms in children. However, young children face difficulty expressing their symptoms due to their limited language abilities. METHODS: The balance of study and patient group evaluated with computer dynamic posturography, single-leg stance test with eyes closed and regular Head Impulse Test. The study group was assessed once again after the insertion of a ventilation tube two months later. RESULTS: In the Sensory Organization Test, the scores for conditions 5, 6, and composite equilibrium of the preoperative patient group were notably lower compared with both the control and postoperative patient groups (p < 0.05). Additionally, a significant correlation was found between single-leg stance test with eyes closed results and conditions 5, 6, and composite equilibrium scores. CONCLUSION: The impact of OME on the vestibular system is negative. This effect can be objectively assessed using Computer Dynamic Posturography and following tube insertion, there is a notable improvement in vestibular function. Furthermore, the single-leg stance (SLS) test with eyes closed has shown its reliability in assessing balance disorders, notably in children with OME. LEVEL OF EVIDENCE: Level 2 Laryngoscope, 2024.

Histaminergic System and Vestibular Function in Normal and Pathological Conditions.

Most neurotransmitter systems are represented in the central and peripheral vestibular system and are thereby involved both in normal vestibular signal processing and the pathophysiology of vestibular disorders. However, there is a special relationship between the vestibular system and the histaminergic system. The purpose of this review is to document how the histaminergic system interferes with normal and pathological vestibular function. In particular, we will discuss neurobiological mechanisms such as neuroinflammation that involve histamine to modulate and allow restoration of balance function in the situation of a vestibular insult. These adaptive mechanisms represent targets of histaminergic pharmacological compounds capable of restoring vestibular function in pathological situations. The clinical use of drugs targeting the histaminergic system in various vestibular disorders is critically discussed.

Sensory Organization and Postural Control Strategies in Individuals With Mild and Moderate-to-Severe Forward Head Posture: A Comparative Study.

OBJECTIVE: This study aimed to compare sensory organization test and postural control strategies between individuals with mild and moderate-to-severe forward head posture (FHP). METHODS: A sensory organization test (SOT) was performed in 6 conditions using computerized dynamic posturography, to assess postural control. Equilibrium scores representing overall balance, strategy analysis to assess ankle vs hip strategy dominance, and sensory analysis (Somatosensory, visual, vestibular, visual preference ratio) as an indicator of the use of sensory systems were obtained. RESULTS: Our results revealed a significant difference between the 2 groups in terms of equilibrium score (P < .05) and strategy scores (P < .05) in conditions of 4 to 6 of the SOT. The results of sensory analysis of SOT showed visual and vestibular ratios were significantly different between the 2 study groups (P < .05), but somatosensory and visual preference ratios were not significantly different between these 2 groups (P > .05). CONCLUSION: Individuals with moderate-to-severe FHP swayed more in comparison with mild FHP ones in conditions with the Sway-referenced platform of the SOT. They tended to rely on the hip strategy more than the ankle strategy excessively when sensory difficulty increased. Overall, it can be concluded that individuals with moderate-to-severe FHP are more likely to have postural deficits.

Improved Recovery after Vestibular Schwannoma Excision with Intratympanic Gentamicin Prehabilitation.

OBJECTIVE: Translabyrinthine excision of a vestibular schwannoma is associated with acute vestibular failure. Preoperative intratympanic gentamicin (ITG) injections can improve objective balance function after surgery but its clinical benefits remain to be established. METHODS: Adult patients undergoing translabyrinthine removal of a vestibular schwannoma between January 2014 and February 2018 underwent preoperative vestibular function testing. Patients were divided in to 3 groups, those with vestibular function (VF) who received ITG injections, those with VF but did not receive ITG and those with no VF. Groups were compared according to degree of vertigo, length of stay, time to unassisted mobilization, and postoperative anti-emetic consumption. RESULTS: Forty six patients had ITG injections (Group 1), 7 had residual VF but refused treatment (Group 2), 21 had no VF (Group 3). Group 1 had a significant improvement in vertigo over time whereas groups 2 and 3 did not. There was a statistically significant 70% decrease in time to independent mobilization between Group 1 and other groups and a 19% decrease in length of stay in Group 1 compared to other groups although this did not reach statistical significance. Two patients had injection-related complications. Group 1 used less anti-emetics than other groups but this was not statistically significant. CONCLUSION: Preoperative intratympanic gentamicin injection with vestibular rehabilitation exercises is associated with less postoperative vertigo and earlier postoperative mobilization. There was reduced duration of hospitalization and decreased consumption of anti-emetic but not significantly so possibly because of low numbers of patients in the no treatment group. LEVEL OF EVIDENCE: 2 Laryngoscope, 134:3316-3322, 2024.

Midbrain lesion-induced disconjugate gaze: a unifying circuit mechanism of ocular alignment?

BACKGROUND: Disconjugate eye movements are essential for depth perception in frontal-eyed species, but their underlying neural substrates are largely unknown. Lesions in the midbrain can cause disconjugate eye movements. While vertically disconjugate eye movements have been linked to defective visuo-vestibular integration, the pathophysiology and neuroanatomy of horizontally disconjugate eye movements remains elusive. METHODS: A patient with a solitary focal midbrain lesion was examined using detailed clinical ocular motor assessments, binocular videooculography and diffusion-weighted MRI, which was co-registered to a high-resolution cytoarchitectonic MR-atlas. RESULTS: The patient exhibited both vertically and horizontally disconjugate eye alignment and nystagmus. Binocular videooculography showed a strong correlation of vertical and horizontal oscillations during fixation but not in darkness. Oscillation intensities and waveforms were modulated by fixation, illumination, and gaze position, suggesting shared visual- and vestibular-related mechanisms. The lesion was mapped to a functionally ill-defined area of the dorsal midbrain, adjacent to the posterior commissure and sparing nuclei with known roles in vertical gaze control. CONCLUSION: A circumscribed region in the dorsal midbrain appears to be a key node for disconjugate eye movements in both vertical and horizontal planes. Lesioning this area produces a unique ocular motor syndrome mirroring hallmarks of developmental strabismus and nystagmus. Further circuit-level studies could offer pivotal insights into shared pathomechanisms of acquired and developmental disorders affecting eye alignment.

Is activation of the vestibular system by electromagnetic induction a possibility in an MRI context?

In recent years, an increasing number of studies have discussed the mechanisms of vestibular activation in strong magnetic field settings such as occur in a magnetic resonance imaging scanner environment. Amid the different hypotheses, the Lorentz force explanation currently stands out as the most plausible mechanism, as evidenced by activation of the vestibulo-ocular reflex. Other hypotheses have largely been discarded. Nonetheless, both human data and computational modeling suggest that electromagnetic induction could be a valid mechanism which may coexist alongside the Lorentz force. To further investigate the induction hypothesis, we provide, herein, a first of its kind dosimetric analysis to estimate the induced electric fields at the vestibular system and compare them with what galvanic vestibular stimulation would generate. We found that electric fields strengths from induction match galvanic vestibular stimulation strengths generating vestibular responses. This review examines the evidence in support of electromagnetic induction of vestibular responses, and whether movement-induced time-varying magnetic fields should be further considered and investigated.

Does sleep quality affect balance? The perspective from the somatosensory, vestibular, and visual systems.

OBJECTIVE: Previous studies have focused on the balance system's involvement in sleep deprivation or disorders. This study investigated how daily routine sleep quality affects the balance system of people without sleep deprivation or diagnosed sleep disorders. METHODS: The study included 45 participants with a BMI score of <25. The PSQI was used to determine sleep quality. The SOT, HS-SOT, and ADT evaluated the vestibular system's functionality. RESULTS: In SOT, condition 3, 4, 5, and 6 composite scores, VIS and VEST composite balance scores, and HS-SOT 5 scores were lower in the HPSQI group. At the same time, there is a statistically significant negative correlation between these scores and PSQI scores. CONCLUSION: Poor sleep quality may be a factor influencing the balance system. Sleep quality affects the visual and vestibular systems rather than the somatosensory system. The population should be made aware of this issue, and clinicians should consider the potential impact of sleep quality when evaluating the balance system.

CHD7 and SOX2 act in a common gene regulatory network during mammalian semicircular canal and cochlear development.

Inner ear morphogenesis requires tightly regulated epigenetic and transcriptional control of gene expression. CHD7, an ATP-dependent chromodomain helicase DNA-binding protein, and SOX2, an SRY-related HMG box pioneer transcription factor, are known to contribute to vestibular and auditory system development, but their genetic interactions in the ear have not been explored. Here, we analyzed inner ear development and the transcriptional regulatory landscapes in mice with variable dosages of Chd7 and/or Sox2. We show that combined haploinsufficiency for Chd7 and Sox2 results in reduced otic cell proliferation, severe malformations of semicircular canals, and shortened cochleae with ectopic hair cells. Examination of mice with conditional, inducible Chd7 loss by Sox2CreER reveals a critical period (~E9.5) of susceptibility in the inner ear to combined Chd7 and Sox2 loss. Data from genome-wide RNA-sequencing and CUT&Tag studies in the otocyst show that CHD7 regulates Sox2 expression and acts early in a gene regulatory network to control expression of key otic patterning genes, including Pax2 and Otx2. CHD7 and SOX2 directly bind independently and cooperatively at transcription start sites and enhancers to regulate otic progenitor cell gene expression. Together, our findings reveal essential roles for Chd7 and Sox2 in early inner ear development and may be applicable for syndromic and other forms of hearing or balance disorders.

NADPH Oxidase 3: Beyond the Inner Ear.

Reactive oxygen species (ROS) were formerly known as mere byproducts of metabolism with damaging effects on cellular structures. The discovery and description of NADPH oxidases (Nox) as a whole enzyme family that only produce this harmful group of molecules was surprising. After intensive research, seven Nox isoforms were discovered, described and extensively studied. Among them, the NADPH oxidase 3 is the perhaps most underrated Nox isoform, since it was firstly discovered in the inner ear. This stigma of Nox3 as "being only expressed in the inner ear" was also used by me several times. Therefore, the question arose whether this sentence is still valid or even usable. To this end, this review solely focuses on Nox3 and summarizes its discovery, the structural components, the activating and regulating factors, the expression in cells, tissues and organs, as well as the beneficial and detrimental effects of Nox3-mediated ROS production on body functions. Furthermore, the involvement of Nox3-derived ROS in diseases progression and, accordingly, as a potential target for disease treatment, will be discussed.