RESUMO
AIM: To characterize vestibular recovery in a mouse model of unilateral labyrinthotomy under local AAT and dexamethasone treatment. BACKGROUND: Alpha1-antitrypsin (AAT) is a circulating tissue-protective molecule that rises during inflammatory conditions and promotes inflammatory resolution. Its local concentration in human perilymph inversely correlates with the severity of inner ear dysfunction; concomitantly, mice that overexpress AAT and undergo inner ear trauma rapidly restore vestibular function. Locally applied AAT has yet to be examined in this context, nor has it been directly compared with anti-inflammatory corticosteroid treatment. METHODS: Wild-type mice C57BL/6 underwent a unilateral inner ear injury. Nine microliters of saline, clinical-grade AAT (180 µg/site), dexamethasone (4 mg/site), or both were applied locally on Days 0, 1, and 2 (n = 5/group). Vestibular function was assessed for 7 days. An in vitro human epithelial gap closure assay was performed using A549 cells in the presence of AAT and/or dexamethasone. RESULTS: Upon labyrinthotomy, all groups displayed severe vestibular dysfunction. Saline-treated mice showed the longest impairment. That group and the dexamethasone group displayed partial to no recovery, while AAT-treated mice exhibited complete recovery within 7 days; at this time point, dexamethasone-treated mice exhibited 50% recovery. Objective vestibular testing showed similar outcomes. In vitro, cotreatment with AAT and dexamethasone resulted in a gap closure dynamic that was superior to AAT alone at 6 h and superior to DEX alone at 48 h. CONCLUSION: Locally applied AAT treatment is superior to locally applied dexamethasone in promoting vestibular recovery in vivo. Ongoing studies are exploring the potential advantages of AAT combined with early low-dose dexamethasone therapy.
Assuntos
Dexametasona , Camundongos Endogâmicos C57BL , alfa 1-Antitripsina , Animais , Camundongos , Dexametasona/administração & dosagem , Dexametasona/uso terapêutico , alfa 1-Antitripsina/administração & dosagem , Doenças Vestibulares/tratamento farmacológico , Doenças Vestibulares/etiologia , Anti-Inflamatórios/administração & dosagem , Anti-Inflamatórios/farmacologia , Orelha Interna/efeitos dos fármacos , Modelos Animais de Doenças , Recuperação de Função Fisiológica/efeitos dos fármacos , Vestíbulo do Labirinto/efeitos dos fármacos , Vestíbulo do Labirinto/lesões , Humanos , MasculinoRESUMO
Gravity is a pervasive environmental stimulus, and accurate graviception is required for optimal spatial orientation and postural stability. The primary graviceptors are the vestibular organs, which include angular velocity (semicircular canals) and linear acceleration (otolith organs) sensors. Graviception is degraded in patients with vestibular damage, resulting in spatial misperception and imbalance. Since minimal therapy is available for these patients, substantial effort has focused on developing a vestibular prosthesis or vestibular implant (VI) that reproduces information normally provided by the canals (since reproducing otolith function is very challenging technically). Prior studies demonstrated that angular eye velocity responses could be driven by canal VI-mediated angular head velocity information, but it remains unknown whether a canal VI could improve spatial perception and posture since these behaviors require accurate estimates of angular head position in space relative to gravity. Here, we tested the hypothesis that a canal VI that transduces angular head velocity and provides this information to the brain via motion-modulated electrical stimulation of canal afferent nerves could improve the perception of angular head position relative to gravity in monkeys with severe vestibular damage. Using a subjective visual vertical task, we found that normal female monkeys accurately sensed the orientation of the head relative to gravity during dynamic tilts, that this ability was degraded following bilateral vestibular damage, and improved when the canal VI was used. These results demonstrate that a canal VI can improve graviception in vestibulopathic animals, suggesting that it could reduce the disabling perceptual and postural deficits experienced by patients with severe vestibular damage.SIGNIFICANCE STATEMENT Patients with vestibular damage experience impaired vision, spatial perception, and balance, symptoms that could potentially respond to a vestibular implant (VI). Anatomic features facilitate semicircular canal (angular velocity) prosthetics but inhibit approaches with the otolith (linear acceleration) organs, and canal VIs that sense angular head velocity can generate compensatory eye velocity responses in vestibulopathic subjects. Can the brain use canal VI head velocity information to improve estimates of head orientation (e.g., head position relative to gravity), which is a prerequisite for accurate spatial perception and posture? Here we show that a canal VI can improve the perception of head orientation in vestibulopathic monkeys, results that are highly significant because they suggest that VIs mimicking canal function can improve spatial orientation and balance in vestibulopathic patients.
Assuntos
Orientação Espacial , Próteses e Implantes , Vestíbulo do Labirinto/lesões , Algoritmos , Animais , Meato Acústico Externo , Eletrodos Implantados , Movimentos Oculares , Feminino , Gravitação , Movimentos da Cabeça , Macaca mulatta , Postura , Reflexo Vestíbulo-Ocular/fisiologiaRESUMO
Unilateral damage to the inner ear results in an acute vestibular syndrome, which is compensated within days to weeks due to adaptive cerebral plasticity. This process, called central vestibular compensation (VC), involves a wide range of functional and structural mechanisms at the cellular and network level. The short-term dynamics of whole-brain functional network recruitment and recalibration during VC has not been depicted in vivo. The purpose of this study was to investigate the interplay of separate and distinct brain regions and in vivo networks in the course of VC by sequential [18F]-FDG-PET-based statistical and graph theoretical analysis with the aim of revealing the metabolic connectome before and 1, 3, 7, and 15 days post unilateral labyrinthectomy (UL) in the rat. Temporal changes in metabolic brain connectivity were determined by Pearson's correlation (|r| > 0.5, p < 0.001) of regional cerebral glucose metabolism (rCGM) in 57 segmented brain regions. Metabolic connectivity analysis was compared to univariate voxel-wise statistical analysis of rCGM over time and to behavioral scores of static and dynamic sensorimotor recovery. Univariate statistical analysis revealed an ipsilesional relative rCGM decrease (compared to baseline) and a contralesional rCGM increase in vestibular and limbic networks and an increase in bilateral cerebellar and sensorimotor networks. Quantitative analysis of the metabolic connections showed a maximal increase from baseline to day 3 post UL (interhemispheric: 2-fold, ipsilesional: 3-fold, contralesional: 12-fold) and a gradual decline until day 15 post UL, which paralleled the dynamics of vestibular symptoms. In graph theoretical analysis, an increase in connectivity occurred especially within brain regions associated with brainstem-cerebellar and thalamocortical vestibular networks and cortical sensorimotor networks. At the symptom peak (day 3 post UL), brain networks were found to be organized in large ensembles of distinct and highly connected hubs of brain regions, which separated again with progressing VC. Thus, we found rapid changes in network organization at the subcortical and cortical level and in both hemispheres, which may indicate an initial functional substitution of vestibular loss and subsequent recalibration and reorganization of sensorimotor networks during VC.
Assuntos
Adaptação Fisiológica , Encéfalo/diagnóstico por imagem , Plasticidade Neuronal , Doenças Vestibulares/diagnóstico por imagem , Vestíbulo do Labirinto/lesões , Animais , Ácido Arsanílico/toxicidade , Encéfalo/metabolismo , Encéfalo/fisiopatologia , Conectoma , Fluordesoxiglucose F18 , Glucose/metabolismo , Locomoção/fisiologia , Vias Neurais/diagnóstico por imagem , Vias Neurais/metabolismo , Vias Neurais/fisiopatologia , Nistagmo Patológico/fisiopatologia , Tomografia por Emissão de Pósitrons , Equilíbrio Postural/fisiologia , Compostos Radiofarmacêuticos , Ratos , Doenças Vestibulares/metabolismo , Doenças Vestibulares/fisiopatologiaRESUMO
INTRODUCTION: Etiology of ISSNHL includes cessation of vascular perfusion, viral infection and cochlear membrane injury. Precise location of injury should be defined for a target-oriented treatment. Vestibular complaints in ISSNHL are hypothesized as involvement of vestibule. Vestibular complaints can be either due to involvement of inner ear or neural tract at any level. OBJECTIVES: In the present study we aimed to demonstrate involvement of vestibular organs in the absence of vestibular symptoms. It was aimed to evaluate superior and inferior vestibular neural pathways. METHODS: c-vemp and o-vemp were applied to patients suffering ISSNHL without vertigo. Pure tone averages, audiogram configurations, degree of hearing loss were analyzed. Latencies of P1 and N1 waves, amplitudes of P1-N1 waves were evaluated. Asymmetrical vemp wave patterns were compared between two ears regarding difference of PTA. RESULTS: Latencies of c-vemp waves were longer and amplitudes were smaller. o-vemp parameters were similar on both sides. Positive correlation was observed between c-vemp latencies and degree hearing loss. CONCLUSION: Inferior vestibular nerve pathway is affected in the absence of vertigo in ISSNHL with spared superior vestibular nerve pathway. Damage in IVN pathway correlates with degree of ISSNHL.
Assuntos
Orelha Interna/patologia , Perda Auditiva Neurossensorial/patologia , Perda Auditiva Súbita/patologia , Potenciais Evocados Miogênicos Vestibulares , Nervo Vestibular/patologia , Vestíbulo do Labirinto/lesões , Adulto , Idoso , Audiometria , Estudos Transversais , Feminino , Perda Auditiva Neurossensorial/fisiopatologia , Perda Auditiva Súbita/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Vertigem , Nervo Vestibular/fisiopatologia , Vestíbulo do Labirinto/inervação , Vestíbulo do Labirinto/patologiaRESUMO
Transient vestibular organ deafferentation, such that is caused by traumatic tissue injury, is presently addressed by corticosteroid therapy. However, restoration of neurophysiological properties is rarely achieved. Here, it was hypothesized that the tissue-protective attributes of α1-antityrpsin (AAT) may promote restoration of neuronal function. Inner ear injury was inflicted by unilateral labyrinthotomy in wild-type mice and in mice overexpressing human AAT. A 2-week-long assessment of vestibular signs followed. All animals responded with peak vestibular dysfunction scores within 4â¯h after local trauma. While wild-type animals displayed partial or no recovery across 7â¯days post-injury, AAT-rich group exhibited early recovery: from behavioral score 9-out-of-9 at peak to 4.8⯱â¯0.44 (mean⯱â¯SD) within 8â¯h from injury, a time when wild-type mice scored 8.6⯱â¯0.54 (pâ¯<â¯0.0001), and from vestibular score 15-out-of-15 to 7.8⯱â¯2.2 within 24â¯h, when wild-type mice scored 13.0⯱â¯2.0 (pâ¯<â¯0.01). Thus, recovery and functional normalisation of an injured vestibular compartment is achievable without corticosteroid therapy; expedited tissue repair processes appear to result from elevated circulating AAT levels. This study lays the foundation for exploring the molecular and cellular mediators of AAT within the repair processes of the delicate microscopic structures of the vestibular end organ.
Assuntos
Vestíbulo do Labirinto/fisiopatologia , Cicatrização/fisiologia , alfa 1-Antitripsina/metabolismo , Animais , Modelos Animais de Doenças , Orelha Interna/lesões , Orelha Interna/fisiopatologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Vestíbulo do Labirinto/lesões , alfa 1-Antitripsina/fisiologiaRESUMO
AIMS: Although the vestibular system has been widely investigated over the past 50 years, there is still an unsolved mystery. Some special vestibular afferent (SVA) neurons responding to both rotation and linear force were found through neurophysiological techniques, however, the sensory overlap mechanism of SVA neurons is still unclear, which may be closely related to vestibular-related diseases. MATERIALS AND METHODS: To address the above-mentioned problem, a cupula buoyancy theory was established in the present study, where SVA neurons were considered semicircular canal afferent (SCCA) neurons. Then labyrinth anatomy and neural response dynamics of vestibular afferent neurons in chinchilla were investigated through vestibular labyrinth reconstruction and single unit recording technique, respectively. KEY FINDINGS: We analyzed the deflections of cupulae under multiple conditions with the help of Amira Software and predicted the neural response law of SCCA neurons to linear force based on the cupula buoyancy theory. Data analysis confirmed that the basic response characteristic of SVA neurons had no significant difference to those of SCCA neurons, but were significantly different from those of otolith afferent neurons. Further, the actual responses of SVA neurons to linear force are completely consistent with our predictions. These results strongly suggest that SVA neurons actually are SCCA neurons, and the cupula buoyancy theory is the key to the sensory overlap mechanism of SCCA neurons. SIGNIFICANCE: Our study revealed the real identity of SVA neurons and provided a reasonable mechanism for sensory overlap of rotation and linear force, which improved our understanding about the vestibular system.
Assuntos
Neurônios Aferentes/fisiologia , Rotação , Sensação/fisiologia , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/fisiologia , Animais , Chinchila , Feminino , Movimentos da Cabeça , Modelos Anatômicos , Membrana dos Otólitos/fisiologia , Canais Semicirculares/fisiologia , Vestíbulo do Labirinto/anatomia & histologiaRESUMO
Following partial or total loss of peripheral vestibular inputs, a phenomenon called central vestibular compensation takes place in the hours and days following the injury. This neuroplasticity process involves a mosaic of profound rearrangements within the brain stem vestibular nuclei. Among them, the setting of a new neuronal network is maybe the most original and unexpected, as it involves an adult reactive neurogenesis in a brain area not reported as neurogenic so far. Both the survival and functionality of this newly generated neuronal network will depend on its integration to pre-existing networks in the deafferented structure. Far from being aberrant, this new structural organization allows the use of inputs from other sensory modalities (vision and proprioception) to promote the restoration of the posture and equilibrium. We choose here to detail this model, which does not belong to the traditional niches of adult neurogenesis, but it is the best example so far of the reparative role of the adult neurogenesis. Not only it represents an original neuroplasticity mechanism, interesting for basic neuroscience, but it also opens new medical perspectives for the development of therapeutic approaches to alleviate vestibular disorders.
TITLE: Le cerveau adulte produit de nouveaux neurones pour restaurer l'équilibre après une perte vestibulaire. ABSTRACT: Un phénomène appelé « compensation vestibulaire ¼ se produit après une atteinte vestibulaire périphérique. Ce processus, qui permet un retour progressif de l'équilibre, se produit principalement au sein des noyaux vestibulaires du tronc cérébral, et met en jeu une mosaïque de réarrangements structurels. Parmi ceux-ci, la neurogenèse vestibulaire réactionnelle (NGVR) adulte est peut-être la plus inattendue, car elle se produit dans une région du cerveau qui n'a jamais été signalée auparavant comme neurogène. La survie et la fonctionnalité de ce réseau neuronal nouvellement généré dépendent de son intégration dans les réseaux préexistants des noyaux désafférentés. Cette organisation permet au cerveau d'utiliser les apports d'autres modalités sensorielles pour faciliter le rétablissement de la posture et de l'équilibre. C'est à ce jour le meilleur exemple du rôle réparateur de la neurogenèse adulte. Ces observations soulèvent de nombreuses questions sur la pertinence physiologique de la NGVR.
Assuntos
Encéfalo/citologia , Neurogênese/fisiologia , Neurônios/fisiologia , Postura/fisiologia , Doenças Vestibulares/reabilitação , Núcleos Vestibulares/lesões , Adulto , Células-Tronco Adultas/citologia , Células-Tronco Adultas/fisiologia , Animais , Encéfalo/fisiologia , Humanos , Células-Tronco Neurais/fisiologia , Plasticidade Neuronal/fisiologia , Doenças Vestibulares/fisiopatologia , Núcleos Vestibulares/patologia , Núcleos Vestibulares/fisiologia , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiologiaRESUMO
BACKGROUND: Cochlear implantation (CI) procedure carries the potential risk for vestibular system insult or stimulation with resultant dysfunction due to its proximity to the cochlea. The vestibular system plays an essential role in crucial tasks such as postural control, gaze stabilization and spatial orientation. RESEARCH QUESTION: How does standard cochlear implantation influence postural stability in patients with hearing loss? METHODS: The study included 21 individuals (age 51 ± 18 years) qualified to undergo CI due to severe or profound hearing loss. Participants were qualified for both groups by a physician based on an interview, an otoneurological examination and vestibular tests. The first group included patients without vestibular dysfunction, whereas the other group consisted of persons with vestibular dysfunction. The research methodology included medical examinations, anthropometric measurements and stabilometry on the Biodex Balance System SD (BBS) platform. The examinations were carried out twice, i.e. prior to and 3 months post implantation. The recorded data was compared between the first and the second examination using a non-parametric Wilcoxon test. The analysis of variance (ANOVA) and Tukey's post-hoc HSD unequal sample sizes were performed for patients with and without vestibular dysfunction. RESULTS AND SIGNIFICANCE: Study showed that 52.4% of the participants obtained results within the norm, while 47.6% scored below it. The comparison of stability indices of the examined individuals, with and without vestibular dysfunction, did not reveal statistically significant differences. The only difference was the anterior-posterior stability index assessed in static conditions. Three months after the implantation, no changes in the majority of indices were noted, with the exception of anterior-posterior stability index, which improved following the implantation. CI does not affect postural stability changes in the study participants.
Assuntos
Implante Coclear/efeitos adversos , Implantes Cocleares/efeitos adversos , Perda Auditiva , Equilíbrio Postural/fisiologia , Adulto , Idoso , Análise de Variância , Feminino , Perda Auditiva/fisiopatologia , Perda Auditiva/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Vestíbulo do Labirinto/lesõesRESUMO
The role of the otoliths in mammals in the normal angular vestibuloocular reflex (VOR) was characterized in an accompanying study based on the Otopetrin1 (Otop1) mouse, which lacks functioning otoliths because of failure to develop otoconia but seems to have otherwise normal peripheral anatomy and neural circuitry. That study showed that otoliths do not contribute to the normal horizontal (rotation about Earth-vertical axis parallel to dorso-ventral axis) and vertical (rotation about Earth-vertical axis parallel to interaural axis) angular VOR but do affect gravity context-specific VOR adaptation. By using these animals, we sought to determine whether the otoliths play a role in the angular VOR after unilateral labyrinthectomy when the total canal signal is reduced. In five Otop1 mice and five control littermates we measured horizontal and vertical left-ear-down and right-ear-down sinusoidal VOR (0.2-10 Hz, 20-100°/s) during the early (3-5 days) and plateau (28-32 days) phases of compensation after unilateral labyrinthectomy and compared these measurements with baseline preoperative responses from the accompanying study. From similar baselines, acute gain loss was ~25% less in control mice, and chronic gain recovery was ~40% more in control mice. The acute data suggest that the otoliths contribute to the angular VOR when there is a loss of canal function. The chronic data suggest that a unilateral otolith signal can significantly improve angular VOR compensation. These data have implications for vestibular rehabilitation of patients with both canal and otolith loss and the development of vestibular implants, which currently only mimic the canals on one side. NEW & NOTEWORTHY This is the first study examining the role of the otoliths (defined here as the utricle and saccule) on the acute and chronic angular vestibuloocular reflex (VOR) after unilateral labyrinthectomy in an animal model in which the otoliths are reliably inactivated and the semicircular canals preserved. This study shows that the otolith signal is used to augment the acute angular VOR and help boost VOR compensation after peripheral injury.
Assuntos
Membrana dos Otólitos/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Doenças Vestibulares/fisiopatologia , Vestíbulo do Labirinto , Animais , Humanos , Masculino , Proteínas de Membrana , Camundongos , Camundongos Knockout , Modelos Animais , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/cirurgiaRESUMO
Postural instability is a cardinal indicator of concussion. Assessments of the postural control system range from clinical to laboratory tests that assess the balance of the individual. In a previous article regarding clinical assessment of balance in adults with concussion, we reviewed the importance of balance as a component in concussion evaluations. The purpose of this review article is to update the information previously published in 2014. Since 2014, research has provided evidence for the incorporation of dynamic methods for evaluating balance postconcussion with particular emphasis on sensory system integration and dual tasking. Therefore, this review will examine the current state of knowledge on how concussion injuries affect postural control, advancements in evaluating balance postconcussion, such as novel eye-tracking techniques, and current recommendations for best practices for balance assessment.
Assuntos
Concussão Encefálica/diagnóstico , Exame Neurológico/métodos , Equilíbrio Postural , Transtornos de Sensação/diagnóstico , Adulto , Terapia por Exercício , Seguimentos , Humanos , Doença de Meniere/diagnóstico , Doença de Meniere/etiologia , Vestíbulo do Labirinto/lesõesRESUMO
Rehabilitation for individuals after mild traumatic brain injury (mTBI) or concussion requires emphasis on both cognitive and physical rest, with a gradual return to activity including sports. As the client becomes more active, the rehabilitation professional should pay close attention to symptoms associated with mTBI, such as headache, dizziness, nausea, and difficulty concentrating. The systematic approach to return to play provided by the Berlin Consensus Statement on Concussion in Sport can apply to adults with mTBI. This protocol calls for gradually increasing the intensity of physical activity while attending to postconcussion symptoms. During the incident that led to an mTBI, the injured individual may incur injuries to the vestibular and balance system that are best addressed by professionals with specific training in vestibular rehabilitation, most commonly physical therapists. Benign paroxysmal positional vertigo is a condition in which otoconia particles in the inner ear dislodge into the semicircular canals, resulting in severe vertigo and imbalance. This condition frequently resolves in a few sessions with a vestibular physical therapist. In conditions such as gaze instability, motion sensitivity, impaired postural control, and cervicogenic dizziness, improvement is more gradual and requires longer follow-up with a physical therapist and a home exercise program. In all of the above-stated conditions, it is essential to consider that a patient with protracted symptoms of mTBI or postconcussion syndrome will recover more slowly than others and should be monitored for symptoms throughout the intervention.
Assuntos
Traumatismos em Atletas/reabilitação , Concussão Encefálica/reabilitação , Lesões Encefálicas Traumáticas/reabilitação , Assistentes de Fisioterapeutas , Adulto , Traumatismos em Atletas/diagnóstico , Concussão Encefálica/diagnóstico , Lesões Encefálicas Traumáticas/diagnóstico , Terapia Combinada , Consenso , Humanos , Equipe de Assistência ao Paciente , Síndrome Pós-Concussão/diagnóstico , Síndrome Pós-Concussão/reabilitação , Prognóstico , Descanso , Volta ao Esporte , Vestíbulo do Labirinto/lesõesRESUMO
The European Society for Clinical Evaluation of Balance Disorders - ESCEBD - Executive Committee meets yearly to identify and address clinical equilibrium problems that are not yet well understood. This particular discussion addressed "discordances" (defined as "lack of agreement") in clinical assessment. Sometimes there is disagreement between a clinical assessment and measured abnormality (ies); sometimes the results within the assessment do not agree. This is sometimes thought of as "malingering" or an attempt to exaggerate what is wrong, but this is not always the case. The Committee discussed the clinical significance of unexpected findings in a patient's assessment. For example intraposturographic discordances sometimes exhibit findings (eg performance on more difficult trials may sometimes be better than on simpler trials). This can be suggestive of malingering, but in some situations can be a legitimate finding. The extreme malingerer and the genuine patient are at opposite ends of a spectrum but there are many variations along this spectrum and clinicians need to be cautious, as a posturography assessment may or may not be diagnostically helpful. Sometimes there is poor correlation between symptom severity and test results. Interpretation of posturography performance can at times be difficult and a patient's results must be correlated with clinical findings without stereotyping the patient. It is only in this situation that assessment in a diagnostic setting can be carried out in an accurate and unbiased manner.
Assuntos
Equilíbrio Postural/fisiologia , Postura/fisiologia , Vestíbulo do Labirinto/lesões , Humanos , Vertigem/diagnóstico , Vertigem/etiologia , Testes de Função Vestibular/métodos , Vestíbulo do Labirinto/fisiopatologiaRESUMO
BACKGROUND: The vestibular lesion (VL) is required to examine the physiological function of the vestibular system in animals. Toxic chemicals or electrical apparatus have been used for the VL, however, they are not ideal as they have low specificity, and can result in unintended damage, and systemic toxic effect. NEW METHOD: Localized vibration-induced VL, using an ultrasonicator, is expected to overcome the problems associated with chemical and electrical lesions. Thus, we examined the effect of the ultrasonication on the VL from the aspects of both the physiological function and histology in the present study. RESULTS: and Comparison with Existing Method(s) Complete VL, which was evaluated by deterioration of swimming skills, righting reflex, and body stability, was induced using an ultrasonicator or electrical apparatus. Histological evaluation shows that hair cell layers in the saccule and utricle were completely destroyed in both methods Furthermore, significant drop in body mass was observed in VL. However, abscess at the cranial base was observed in VL induced by the electrical apparatus in ICR mice. Complete chemically-induced VL was observed in C57BL/6J but not ICR mice, and systemic leakage of the toxic chemicals (arsenic) was not detectable even 1day after surgery. CONCLUSIONS: Compared to the electrical apparatus, the ultrasonicator is useful for inducing VL in ICR and C57BL/6J mice, as it results in less non-specific damage. Toxic chemicals can be used for inducing VL in C57BL/6J mice; however, this method does not ensure complete disruption of the hair cells in the saccule and utricle.
Assuntos
Modelos Animais de Doenças , Doenças Vestibulares , Vestíbulo do Labirinto/lesões , Animais , Ácido Arsanílico , Tamanho Corporal , Masculino , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos ICR , Estimulação Física/efeitos adversos , Estimulação Física/métodos , Especificidade da Espécie , Ultrassom , Doenças Vestibulares/diagnóstico por imagem , Doenças Vestibulares/patologia , Doenças Vestibulares/fisiopatologia , Testes de Função Vestibular , Vestíbulo do Labirinto/diagnóstico por imagem , Vestíbulo do Labirinto/patologia , Vestíbulo do Labirinto/fisiopatologia , VibraçãoRESUMO
A consequence of vestibular loss is increased coupling of head-on-trunk motion, particularly in the yaw plane, which adversely affects community mobility in these patients. Inertial sensors may provide a means of better understanding normal decoupling behaviors in community environments, but demonstration of their validity and responsiveness is needed. This paper examined the validity and measurement sensitivity of inertial sensors in quantifying yaw plane head-trunk decoupling during unrestricted and restricted cervical motion conditions in healthy adults. Peak head turn amplitude and velocity, head-trunk coupling, and trunk turn lag were simultaneously measured using wearable inertial sensors and a motion capture system. Agreement between motion capture and the inertial sensors was excellent (intraclass correlation coefficients(2,1) >.75) for all measured outcomes during a static head turn task and for peak head turn velocity and trunk turn lag during a walking task. Cervical collar use significantly reduced head turn amplitude and velocity, and increased coupling of head-on-trunk motion (p<.02). Measurement of head and trunk coordination during gait activities using inertial sensors is valid and feasible. Amplitude and velocity outcomes were most reliable and responsive to experimental alterations in head motion. Using inertial sensors to quantify abnormal kinematics following vestibular loss may provide insights into recovery of head-trunk coordination in these individuals.
Assuntos
Fenômenos Biomecânicos , Cabeça , Tronco , Dispositivos Eletrônicos Vestíveis , Acelerometria , Adolescente , Adulto , Algoritmos , Estudos de Viabilidade , Feminino , Voluntários Saudáveis , Humanos , Masculino , Pessoa de Meia-Idade , Equilíbrio Postural , Vestíbulo do Labirinto/lesões , Adulto JovemRESUMO
Sensorineural hearing loss, ataxia, pyramidal signs, and vestibular deficits characterize superficial siderosis of the central nervous system. This study investigated changes in vestibular function, free radical formation, and phosphorylated cJun expression in the vestibular end organs after middle ear treatment with a ferric chloride (FeCl3) solution. A single injection of 70% FeCl3 solution into the unilateral middle ear cavity caused static vestibular symptoms, such as spontaneous nystagmus and head tilt. Asymmetric expression of c-Fos protein was observed in the bilateral vestibular nuclei and prepositus hypoglossal nuclei within 6 h after injection. Histopathologic examinations revealed partial hair cell loss, degeneration of the supporting stroma, and terminal deoxynucleotidyl transferase dUTP nick end labeling-positive cells in the neuroepithelial layer of the crista ampullaris in FeCl3-treated animals. 5-(And-6)-chloromethyl-2',7'-dichlorodihydrofluorescein diacetate, acetyl ester and diaminofluorescein-2 diacetate fluorescence and immunoreactivity for nitrotyrosine increased markedly in the sensory neuroepithelial layer and nerve bundles of the crista ampullaris after 2 h. Strong immunoreactivity for phospho-cJun and cJun was observed in the type I hair cells of the crista ampullaris 120 h after injection. Thus, a single short-term treatment with a high concentration of FeCl3 in the unilateral middle ear cavity can induce activation of intracellular signals for cJun protein and oxidative stress through the formation of reactive oxygen species and nitric oxide in vestibular sensory receptors, resulting in vestibular dysfunction. These results suggest that activation of intracellular signals for cJun protein and oxidative stress may be a key component of the pathogenesis of vestibular deficits in patients with superficial siderosis.
Assuntos
Cloretos/toxicidade , Orelha Média/efeitos dos fármacos , Compostos Férricos/toxicidade , Vestíbulo do Labirinto/lesões , Animais , Masculino , Óxido Nítrico/biossíntese , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Vestíbulo do Labirinto/metabolismo , Vestíbulo do Labirinto/patologiaRESUMO
Neural circuits are endowed with several forms of intrinsic and synaptic plasticity that could contribute to adaptive changes in behavior, but circuit complexities have hindered linking specific cellular mechanisms with their behavioral consequences. Eye movements generated by simple brainstem circuits provide a means for relating cellular plasticity to behavioral gain control. Here we show that firing rate potentiation, a form of intrinsic plasticity mediated by reductions in BK-type calcium-activated potassium currents in spontaneously firing neurons, is engaged during optokinetic reflex compensation for inner ear dysfunction. Vestibular loss triggers transient increases in postsynaptic excitability, occlusion of firing rate potentiation, and reductions in BK currents in vestibular nucleus neurons. Concurrently, adaptive increases in visually evoked eye movements rapidly restore oculomotor function in wild-type mice but are profoundly impaired in BK channel-null mice. Activity-dependent regulation of intrinsic excitability may be a general mechanism for adaptive control of behavioral output in multisensory circuits.
Assuntos
Movimentos Oculares/fisiologia , Canais de Potássio Ativados por Cálcio de Condutância Alta/fisiologia , Plasticidade Neuronal/fisiologia , Reflexo Vestíbulo-Ocular/fisiologia , Células Receptoras Sensoriais/fisiologia , Núcleos Vestibulares/fisiologia , Animais , Medições dos Movimentos Oculares , Camundongos , Núcleos Vestibulares/citologia , Vestíbulo do Labirinto/lesõesRESUMO
While miniature inertial sensors offer a promising means for precisely detecting, quantifying and classifying animal behaviors, versatile inertial sensing devices adapted for small, freely-moving laboratory animals are still lacking. We developed a standalone and cost-effective platform for performing high-rate wireless inertial measurements of head movements in rats. Our system is designed to enable real-time bidirectional communication between the headborne inertial sensing device and third party systems, which can be used for precise data timestamping and low-latency motion-triggered applications. We illustrate the usefulness of our system in diverse experimental situations. We show that our system can be used for precisely quantifying motor responses evoked by external stimuli, for characterizing head kinematics during normal behavior and for monitoring head posture under normal and pathological conditions obtained using unilateral vestibular lesions. We also introduce and validate a novel method for automatically quantifying behavioral freezing during Pavlovian fear conditioning experiments, which offers superior performance in terms of precision, temporal resolution and efficiency. Thus, this system precisely acquires movement information in freely-moving animals, and can enable objective and quantitative behavioral scoring methods in a wide variety of experimental situations.
Assuntos
Movimentos da Cabeça/fisiologia , Tecnologia sem Fio/instrumentação , Acelerometria/instrumentação , Animais , Comportamento Animal/fisiologia , Fenômenos Biomecânicos , Condicionamento Psicológico/fisiologia , Desenho de Equipamento , Medo/fisiologia , Masculino , Ratos , Ratos Long-Evans , Vestíbulo do Labirinto/lesões , Vestíbulo do Labirinto/fisiopatologiaRESUMO
Unilateral inner ear damage is followed by a rapid behavioural recovery due to central vestibular compensation. In this study, we utilized serial [(18)F]Fluoro-deoxyglucose ([(18)F]FDG)-µPET imaging in the rat to visualize changes in brain glucose metabolism during behavioural recovery after surgical and chemical unilateral labyrinthectomy, to determine the extent and time-course of the involvement of different brain regions in vestibular compensation and test previously described hypotheses of underlying mechanisms. Systematic patterns of relative changes of glucose metabolism (rCGM) were observed during vestibular compensation. A significant asymmetry of rCGM appeared in the vestibular nuclei, vestibulocerebellum, thalamus, multisensory vestibular cortex, hippocampus and amygdala in the acute phase of vestibular imbalance (4 h). This was followed by early vestibular compensation over 1-2 days where rCGM re-balanced between the vestibular nuclei, thalami and temporoparietal cortices and bilateral rCGM increase appeared in the hippocampus and amygdala. Subsequently over 2-7 days, rCGM increased in the ipsilesional spinal trigeminal nucleus and later (7-9 days) rCGM increased in the vestibulocerebellum bilaterally and the hypothalamus and persisted in the hippocampus. These systematic dynamic rCGM patterns during vestibular compensation, were confirmed in a second rat model of chemical unilateral labyrinthectomy by serial [(18)F]FDG-µPET. These findings show that deafferentation-induced plasticity after unilateral labyrinthectomy involves early mechanisms of re-balancing predominantly in the brainstem vestibular nuclei but also in thalamo-cortical and limbic areas, and indicate the contribution of spinocerebellar sensory inputs and vestibulocerebellar adaptation at the later stages of behavioural recovery.
Assuntos
Vias Auditivas/metabolismo , Encéfalo/metabolismo , Plasticidade Neuronal , Núcleos Vestibulares/metabolismo , Vestíbulo do Labirinto/lesões , Animais , Vias Auditivas/diagnóstico por imagem , Encéfalo/diagnóstico por imagem , Fluordesoxiglucose F18 , Glucose/metabolismo , Masculino , Nistagmo Patológico/etiologia , Tomografia por Emissão de Pósitrons , Postura , Ratos , Ratos Sprague-Dawley , Núcleos Vestibulares/diagnóstico por imagem , Vestíbulo do Labirinto/inervaçãoRESUMO
The recognition of head orientation in the adult involves multi-level integration of inputs within the central vestibular circuitry. How the different inputs are recruited during postnatal development remains unclear. We hypothesize that glutamatergic transmission at the vestibular nucleus contributes to developmental registration of head orientations along the vestibulo-olivary pathway. To investigate the maturation profile by which head rotational signals are registered in the brainstem, we used sinusoidal rotations on the orthogonal planes of the three pairs of semicircular canals. Fos expression was used as readout of neurons responsive to the rotational stimulus. Neurons in the vestibular nucleus and prepositus hypoglossal nucleus responded to all rotations as early as P4 and reached adult numbers by P21. In the reticular formation and inferior olive, neurons also responded to horizontal rotations as early as P4 but to vertical rotations not until P21 and P25, respectively. Neuronal subpopulations that distinguish between rotations activating the orthogonally oriented vertical canals were identifiable in the medial and spinal vestibular nuclei by P14 and in the inferior olivary subnuclei IOß and IOK by P25. Neonatal perturbation of glutamate transmission in the vestibular nucleus was sufficient to derange formation of this distribution in the inferior olive. This is the first demonstration that developmental refinement of glutamatergic synapses in the central vestibular circuitry is essential for developmental registration of head rotational signals in the brainstem.
Assuntos
Potenciais Pós-Sinápticos Excitadores , Ácido Glutâmico/fisiologia , Neurônios/fisiologia , Núcleo Olivar/fisiologia , Rotação , Canais Semicirculares/fisiologia , Núcleos Vestibulares/fisiologia , Animais , Maleato de Dizocilpina/administração & dosagem , Antagonistas de Aminoácidos Excitatórios/administração & dosagem , Feminino , Masculino , Vias Neurais/fisiologia , Neurônios/metabolismo , Núcleo Olivar/crescimento & desenvolvimento , Núcleo Olivar/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos , Ratos Sprague-Dawley , Receptores de N-Metil-D-Aspartato/antagonistas & inibidores , Formação Reticular/metabolismo , Formação Reticular/fisiologia , Canais Semicirculares/crescimento & desenvolvimento , Núcleos Vestibulares/crescimento & desenvolvimento , Núcleos Vestibulares/metabolismo , Vestíbulo do Labirinto/lesõesRESUMO
An acute unilateral vestibular lesion leads to a vestibular tone imbalance with nystagmus, head roll tilt and postural imbalance. These deficits gradually decrease over days to weeks due to central vestibular compensation (VC). This study investigated the effects of i.v. N-acetyl-DL-leucine, N-acetyl-L-leucine and N-acetyl-D-leucine on VC using behavioural testing and serial [18F]-Fluoro-desoxyglucose ([18F]-FDG)-µPET in a rat model of unilateral chemical labyrinthectomy (UL). Vestibular behavioural testing included measurements of nystagmus, head roll tilt and postural imbalance as well as sequential whole-brain [18F]-FDG-µPET was done before and on days 1,3,7 and 15 after UL. A significant reduction of postural imbalance scores was identified on day 7 in the N-acetyl-DL-leucine (p < 0.03) and the N-acetyl-L-leucine groups (p < 0.01), compared to the sham treatment group, but not in the N-acetyl-D-leucine group (comparison for applied dose of 24 mg i.v. per rat, equivalent to 60 mg/kg body weight, in each group). The course of postural compensation in the DL- and L-group was accelerated by about 6 days relative to controls. The effect of N-acetyl-L-leucine on postural compensation depended on the dose: in contrast to 60 mg/kg, doses of 15 mg/kg and 3.75 mg/kg had no significant effect. N-acetyl-L-leucine did not change the compensation of nystagmus or head roll tilt at any dose. Measurements of the regional cerebral glucose metabolism (rCGM) by means of µPET revealed that only N-acetyl-L-leucine but not N-acetyl-D-leucine caused a significant increase of rCGM in the vestibulocerebellum and a decrease in the posterolateral thalamus and subthalamic region on days 3 and 7. A similar pattern was found when comparing the effect of N-acetyl-L-leucine on rCGM in an UL-group and a sham UL-group without vestibular damage. In conclusion, N-acetyl-L-leucine improves compensation of postural symptoms after UL in a dose-dependent and specific manner, most likely by activating the vestibulocerebellum and deactivating the posterolateral thalamus.