Brahim Tighilet

Brahim Tighilet
Aix-Marseille Université | AMU · CNRS

Phd

About

76
Publications
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Publications

Publications (76)
Article
Full-text available
Impaired vestibular function induces disabling symptoms such as postural imbalance, impaired locomotion, vestibulo-ocular reflex alteration, impaired cognitive functions such as spatial disorientation, and vegetative deficits. These symptoms show up in sudden attacks in patients with Ménière or neuritis and may lead to emergency hospitalizations. T...
Article
Full-text available
The vestibular system exerts control over various functions through neural pathways that are not yet fully mapped. Functional dysregulations or tissue lesions at different levels of the peripheral and the central vestibular networks can alter these different functions, causing a wide variety of symptoms, ranging from posturo-locomotor alterations t...
Article
Full-text available
Unilateral vestibular lesions induce a vestibular syndrome, which recovers over time due to vestibular compensation. The therapeutic effect of L-Thyroxine (L-T4) on vestibular compensation was investigated by behavioral testing and immunohistochemical analysis in a rat model of unilateral vestibular neurectomy (UVN). We demonstrated that a short-te...
Article
Full-text available
Acute peripheral vestibulopathy leads to a cascade of symptoms involving balance and gait disorders that are particularly disabling for vestibular patients. Vestibular rehabilitation protocols have proven to be effective in improving vestibular compensation in clinical practice. Yet, the underlying neurobiological correlates remain unknown. The aim...
Article
Full-text available
We have previously reported in a feline model of acute peripheral vestibulopathy (APV) that the sudden, unilateral, and irreversible loss of vestibular inputs induces selective overexpression of small conductance calcium-activated potassium (SK) channels in the brain stem vestibular nuclei. Pharmacological blockade of these ion channels by the sele...
Article
Full-text available
Le système vestibulaire possède une remarquable capacité d’autoréparation. La compensation vestibulaire, un modèle de plasticité post-lésionnelle du système nerveux central, se réfère à un ensemble de mécanismes endogènes de neuroplasticité dans les noyaux vestibulaires en réponse à des atteintes du système vestibulaire périphérique et sous-tendant...
Article
Purpose This study was carried out within the framework of a research on the non-medicinal managment of the dizzy patient. In order to carry out an inventory of vestibular rehabilitation practices in France, we conducted this research among practitioners recognized in this exercise. Materials and Methods We conducted a survey using a thoretical qu...
Article
Full-text available
Background Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained spi...
Article
Importance: An infective etiology of acute peripheral vestibulopathy (APV) has long been hypothesized. In the context of coronavirus disease 2019 (COVID-19), we examined the possible comorbidity between these two entities. Objectives: APV is the second most common cause of vestibular disorders and results from a sudden and unilateral loss of ves...
Article
Unilateral vestibular neurectomy (UVN) induces a postural syndrome whose compensation over time is underpinned by multimodal sensory substitution processes. However, at a chronic stage of compensation, UVN rats exhibit an enduring postural asymmetry expressed by an increase in the body weight on the ipsilesional paws. Given the anatomo-functional l...
Article
Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate tha...
Article
Résumé Cette étude a été réalisée afin d’inventorier les pratiques de rééducation vestibulaire en France. Nous avons mené une enquête au moyen d’un questionnaire envoyé à un ensemble de kinésithérapeutes vestibulaires français. Le questionnaire a permis d’explorer différents sujets, tels que la pratique de l’examen clinique et les protocoles de réé...
Preprint
Unilateral vestibular lesions induce a vestibular syndrome, which recovers over time due to vestibular compensation. The therapeutic effect of L-Thyroxine (L-T4) on vestibular compensation was investigated by behavioral testing and immunohistochemical analysis in a rat model of unilateral vestibular neurectomy (UVN). We demonstrated that an acute L...
Preprint
Full-text available
Background : Due to their anti-inflammatory action, corticosteroids are the reference treatment for brain injuries and many inflammatory diseases. However, the benefits of acute corticotherapy are now being questioned, particularly in the case of acute peripheral vestibulopathies (APV), characterized by a vestibular syndrome composed of sustained s...
Preprint
Full-text available
Glutamatergic and GABAergic neurons represent the neural components of the medial vestibular nuclei. We assessed the functional role of glutamatergic and GABAergic neuronal pathways arising from the vestibular nuclei (VN) in the maintenance of gait and balance by optogenetically stimulating the VN in VGluT2-cre and GAD2-cre mice. We demonstrate tha...
Article
We previously revealed adult reactive neurogenesis in deafferented vestibular nuclei following unilateral vestibular neurectomy (UVN) in the feline model. We recently replicated the same surgery in a rodent model and aimed to elucidate the origin and fate of newly generated cells following UVN. We used specific markers of cell proliferation, glial...
Article
Full-text available
Vestibular pathologies are difficult to diagnose. Existing devices make it possible to quantify and follow the evolution of posturo-locomotor symptoms following vestibular loss in static conditions. However, today, there are no diagnostic tools allowing the quantitative and spontaneous analysis of these symptoms in dynamic situations. With this in...
Article
Full-text available
Un phénomène appelé « compensation vestibulaire » 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 ré...
Article
Full-text available
The vestibular system plays a crucial role in maintaining postural balance. Unilateral vestibular lesions result in a typical syndrome characterized by postural imbalance, altered locomotor patterns and gaze stabilization, as well as cognitive and neurovegetative disorders. One of the main difficulties encountered in the development of new anti-ver...
Chapter
Synopsis Adult neurogenesis contributes to plasticity in the brain and is considered to be an important mechanism of vestibular compensation following inner ear lesions. Reactive neurogenesis occurs in the deafferented vestibular nuclei after unilateral vestibular loss and appears to contribute to the functional recovery. Neurogenesis in the hippoc...
Article
Full-text available
Introduction La névrite vestibulaire (NV) est une vestibulopathie périphérique unilatérale aiguë. Elle représente environ 7 % des patients consultant pour des vertiges et se caractérise par un syndrome vestibulaire composé de vertiges, d’un nystagmus oculaire spontané, de troubles posturo-locomoteurs et de symptômes végétatifs. Ces troubles dispara...
Article
Introduction La section unilatérale du nerf vestibulaire (NVU) engendre un syndrome vestibulaire bien connu chez l’Homme et l’animal qui comprend des désordres posturo-locomoteurs, oculomoteurs et cognitifs dont l’expression diminue progressivement avec le temps. À un stade avancé de la compensation, les animaux vestibulo-lésés présentent une asymé...
Article
Full-text available
Introduction Diagnostiquer une pathologie vestibulaire reste toujours difficile. Les dispositifs existants permettent de quantifier et suivre l’évolution des symptômes posturo-locomoteurs en condition statique. Cependant, aujourd’hui il n’existe pas d’outils diagnostiques permettant l’analyse quantitative de ces symptômes dans une situation dynamiq...
Article
Introduction Unilateral vestibular lesion results in a typical syndrome characterized by postural imbalance, alteration of locomotion and gaze stabilization as well as cognitive and neurovegetative disorders. One of the main difficulties encountered in the development of new anti-vertigo drugs is the lack of sensitivity in the evaluation of this sy...
Article
Full-text available
Over the last few decades, several studies have been conducted to identify the mechanisms involved in spontaneous functional recovery following peripheral vestibular damage. Different reactive processes occur at both the central and peripheral levels over the first few hours after the loss of the peripheral vestibular input. The restoration of the...
Article
Full-text available
A central role for damage to cochlear primary afferent synapses has been demonstrated in various auditory pathologies. Similarly, the selective lesioning of primary vestibular synapses may be an underlying cause of peripheral vestibulopathies that cause vertigo and dizziness, for which the pathophysiology is currently unknown. To thoroughly address...
Article
A phenomenon called vestibular compensation occurs after peripheral vestibular loss. This process involves a mosaic of profound structural rearrangements within the vestibular nuclei. Among them, adult reactive neurogenesis is perhaps the most unexpected, as it occurs in a brain area that was never reported as neurogenic before. Both the survival a...
Article
Sudden and complete unilateral loss of peripheral vestibular inputs evokes characteristic vestibular syndrome comprised of posturo-locomotor, oculomotor, vegetative and cognitive symptoms. Subsequently to the vestibular insult, a neurophysiological process called central vestibular compensation promotes the progressive restoration of the posture an...
Article
The vestibular system encodes linear and angular head motion supporting numerous functions from gaze stabilization and postural control, to high-level cortical functions involving spatial cognition, including self-body perception, verticality perception, orientation, navigation and spatial memory. At the brainstem and mesencephalic levels, the vest...
Article
Full-text available
This study is a pharmacokinetic (PK) and pharmacodynamics (PD) approach using betahistine doses levels in unilateral vestibular neurectomized cats (UVN) comparable to those used in humans for treating patients with Menière's disease. The aim is to investigate for the first time oral betahistine administration (0.2 and 2 mg/kg/day) with plasma conce...
Article
Full-text available
Acute vestibular syndrome (AVS) is characterized by severe posturo-locomotor and vestibulo-oculomotor impairment and accompanies several types of peripheral vestibulopathies (PVP). We know very little about its etiology, how its various symptoms are expressed and how it evolves with age. Robust repair capabilities of primary vestibular synapses hav...
Article
Full-text available
Vestibular disorders, by inducing significant posturo-locomotor and cognitive disorders, can significantly impair the most basic tasks of everyday life. Their precise diagnosis is essential to implement appropriate therapeutic countermeasures. Monitoring their evolution is also very important to validate or, on the contrary, to adapt the undertaken...
Data
Supporting information is provided at S1_File.xls. (XLS)
Article
Background: Unilateral vestibular deafferentation syndrome (uVDS) holds a particular place in the vestibular pathology domain. Due to its suddenness, the violence of its symptoms that often result in emergency hospitalization, and its associated original neurophysiological properties, this syndrome is a major source of questioning for the otoneuro...
Article
Background: Both basic and applied studies on the pathophysiology of vestibular disorders are currently impaired by the lack of animal models of controlled vestibular damages. New methods: In the present study, we describe the procedure to achieve a surgical unilateral vestibular neurectomy (UVN) in the rat and evaluate its functional consequenc...
Article
Full-text available
While many studies have been devoted to investigating the homeostatic plasticity triggered by cochlear hearing loss, the cellular and molecular mechanisms involved in these central changes remain elusive. In the present study, we investigated the possibility of reactive neurogenesis after unilateral cochlear nerve section in the cochlear nucleus (C...
Article
Reactive cell proliferation occurs rapidly in the cat vestibular nuclei (VN) after unilateral vestibular neurectomy (UVN) and has been reported to facilitate the recovery of posturo-locomotor functions. Interestingly, whereas animals experience impairments for several weeks, extraordinary plasticity mechanisms take place in the local microenvironme...
Article
Reactive cell proliferation occurs rapidly in the cat vestibular nuclei (VN) after unilateral vestibular neurectomy (UVN) and has been reported to facilitate the recovery of posturo-locomotor functions. Interestingly, whereas animals experience impairments for several weeks, extraordinary plasticity mechanisms take place in the local microenvironme...
Article
Full-text available
Head roll tilt, postural imbalance and spontaneous nystagmus are the main static vestibular deficits observed after an acute unilateral vestibular loss (UVL). In the UVL cat model, these deficits are fully compensated over 6 weeks as the result of central vestibular compensation. N-Acetyl-DL-leucine is a drug prescribed in clinical practice for the...
Article
Full-text available
After unilateral vestibular neurectomy (UVN) many molecular and neurochemical mechanisms underlie the neurophysiological reorganizations occurring in the vestibular nuclei (VN) complex, as well as the behavioral recovery process. As a key regulator, the histaminergic system appears to be a likely candidate because drugs interfering with histamine (...
Article
Strong reactive cell proliferation occurs in the vestibular nuclei after unilateral vestibular neurectomy (UVN). Most of the newborn cells survive, differentiate into glial cells and neurons with GABAergic phenotype, and have been reported to contribute to recovery of the posturo-locomotor functions in adult cats. Because the GABAergic system modul...
Data
Mean total GFAP immuno-positive cell numbers and CE of stereological analysis for estimation of total GFAP immuno-positive cells in the ipsilateral and contralateral vestibular nuclei complexes of the sham and the experimental groups of cats for each survival period tested. Values are mean ± SEM; CE: coefficient of error, GFAP: glial fibrillary aci...
Data
Full-text available
Mean total BrdU immuno-positive cell numbers and CE of stereological analysis for estimation of total BrdU immuno-positive cells in the ipsilateral and contralateral vestibular nuclei complexes of the sham and the experimental groups of cats for each survival period tested. Values are mean ± SEM; CE: coefficient of error, BrdU: 5-bromo-2′deoxyuridi...
Data
Full-text available
Mean total GAD67 immuno-positive cell numbers and CE of stereological analysis for estimation of total GAD67 immuno-positive cells in the ipsilateral and contralateral vestibular nuclei complexes of the sham and the experimental groups of cats for each survival period tested. Values are mean ± SEM; CE: coefficient of error, GAD67: glutamic acid dec...
Article
Full-text available
Functional and reactive neurogenesis and astrogenesis are observed in deafferented vestibular nuclei after unilateral vestibular nerve section in adult cats. The newborn cells survive up to one month and contribute actively to the successful recovery of posturo-locomotor functions. This study investigates whether the nature of vestibular deafferent...
Article
Full-text available
The adult mammal brain is mostly considered as non-neurogenic, except in the subventricular zone of the lateral ventricles and the subgranular zone of the dentate gyrus, where ongoing neurogenesis occurs. However, anti-neurogenic influences can be removed in pathological conditions or after specific injury. That is what happens in a model of unilat...
Article
Contrary to the view of a rigid, hardwired adult central nervous system (CNS) that was commonly accepted up to a few decades ago (Ramon y Cajal, 1928), the adult CNS is now seen as continuously reorganizing throughout the life course. Adaptive plasticity, consisting of both structural reorganization and modifications of the functional properties of...
Article
Full-text available
In physiological conditions, neurogenesis occurs in restricted regions of the adult mammalian brain, giving rise to integrated neurons into functional networks. In pathological or postlesional conditions neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after immediate unilateral vestibular neurecto...
Article
Most patients with unilateral vestibular loss exhibit a similar static and dynamic vestibular syndrome consisting of vestibulo-ocular, posturolocomotor, and perceptive deficits. This vestibular syndrome recovers more or less completely and more or less rapidly over time. One open question is whether recovery mechanisms differ according to vestibula...
Article
The postural, ocular motor, perceptive and neurovegetative syndromes resulting from unilateral vestibular neurectomy (UVN) symptoms could generate a stress and thereby activate the hypothalamo-pituitary-adrenal (HPA) axis. This study was aimed at determining whether UVN causes changes in the activity of the HPA axis, and if so, evaluating the time...
Article
Full-text available
Neurogenesis occurs in some regions of the adult mammalian brain and gives rise to neurons integrated into functional networks. In pathological or postlesional conditions, neurogenesis and astrogenesis can also occur, as demonstrated in the deafferented vestibular nuclei after unilateral vestibular neurectomy in the adult cat. Here we report that i...
Article
Full-text available
Ménière's disease and related disease of the vestibular system are common and debilitating. Current therapy is multi-modal and includes drug therapy and lifestyle adaptations. Unfortunately many of the drugs used in treatment (particularly those used to control nausea) are sedative and hamper the process of vestibular compensation. Although betahis...
Article
This study analysed the effects of betahistine and thioperamide, two histamine H(3) receptor antagonists, on the recovery process after unilateral vestibular neurectomy (UVN) in the cat. In UVN animals untreated or treated with betahistine or thioperamide, recovery was evaluated by recording the horizontal spontaneous nystagmus and the postural and...
Article
Recent findings revealed a reactive neurogenesis after lesions and in several models of disease. After unilateral vestibular neurectomy (UVN), we previously reported gamma-aminobutyric acid (GABA)ergic neurons are upregulated in the vestibular nuclei (VN) in the adult cat. Here, we ask whether this upregulation of GABAergic neurons resulted from a...
Article
To determine how the histaminergic system is implicated in vestibular compensation, we studied the changes in histidine decarboxylase (HDC; the enzyme synthesizing histamine) mRNA regulation in the tuberomammillary (TM) nuclei of cats killed 1 week, 3 weeks and 3 months after unilateral vestibular neurectomy (UVN). We also used one- and two-step bi...
Article
Drugs interacting with the histaminergic system are currently used for vertigo treatment and it was shown in animal models that structural analogues of histamine like betahistine improved the recovery process after vestibular lesion. This study was aimed at determining the possible dose and duration effects of betahistine treatment on histamine tur...
Article
Drugs interfering with the histaminergic system facilitate behavioral recovery after vestibular lesion, likely by increasing histamine turnover and release. The effects of betahistine (structural analogue of histamine) on the histaminergic system were tested by quantifying messenger RNA for histidine decarboxylase (enzyme synthesizing histamine) by...
Article
Recent neurochemical investigations of the central vestibular pathways have demonstrated that several neurotransmitters are involved in various operations required for stabilizing posture and gaze. Neurons of the vestibular nuclei (VN) receive GABAergic inhibitory afferents, and GABAergic neurons distributed throughout the vestibular complex are im...
Article
Histamine is thought to be involved in the recovery of vestibular function as histaminergic medications are effective in vestibular-related syndromes. We conducted studies in the cat to assess the effects of betahistine (a histamine-like substance) on the behavioural recovery process after unilateral vestibular neurectomy (UVN). We also investigate...
Article
Immediate early genes are generally expressed in response to sensory stimulation or deprivation and can be used for mapping brain functional activity and studying the molecular events underlying CNS plasticity. We immunohistochemically investigated Fos protein induction in the cat brainstem after unilateral vestibular neurectomy (UVN), with special...
Article
Post-lesion recovery of vestibular functions is a suitable model for studying adult central nervous system plasticity. The vestibular nuclei complex (VN) plays a major role in the recovery process and neurochemical reorganizations have been described at this brainstem level. The cholinergic system should be involved because administration of cholin...
Article
Subcortical and corticothalamic inputs excite thalamic neurons via a diversity of glutamate receptor subtypes. Differential expression of alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid (AMPA), kainate, and N-methyl-D-aspartate (NMDA) receptor subunits (GluR1-4; GluR5-7; NR1, NR2A-D) on a nucleus- and cell type-specific basis was examined...
Article
Full-text available
In situ hybridization histochemistry and immunocytochemistry were used to study localization and activity-dependent regulation of alpha, beta, gamma, and delta isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII) and their mRNAs in areas 17 and 18 of normal and monocularly deprived adult macaques. CaMKII-alpha is expressed overa...
Article
In situ hybridization histochemistry and immunocytochemistry were used to map distributions of cells expressing mRNAs encoding alpha, beta, gamma, and delta isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/ kainate receptor subunits, (GluR1-7), and N-methyl-D-aspa...
Article
In situ hybridization histochemistry and immunocytochemistry were used to map distributions of cells expressing mRNAs encoding alpha, beta, gamma, and delta isoforms of type II calcium/calmodulin-dependent protein kinase (CaMKII), alpha-amino-3-hydroxy-5-methyl-4-isoxazoleproprionate (AMPA)/kainate receptor subunits, (GluR1-7), and N-methyl-D-aspar...
Article
Histamine is likely involved in vestibular function recovery since histaminergic medications are effective in vestibular-related syndromes. We investigated the histamine immunoreactivity changes after unilateral vestibular neurectomy and the effects of betahistine (a partial histamine H1 receptor agonist and an histamine H3 receptor antagonist) and...
Article
The histaminergic projection in the cat brain originates from neurones located in the tuberomammillary nucleus. The distribution of histaminergic axonal fibres was investigated immunohistochemically in the vestibular nuclei of the cat using an antibody to histamine. Labelled fibres were sparsely distributed in the whole vestibular nuclei complex an...
Article
Vision has long been recognized as a sensorimotor system which plays a major role in substitution for functional deficits induced by unilateral or bilateral exclusion of primary vestibular afferents. Little is known, however, about the post-lesion influence of visual inputs on the recovery of posturo-kinetic balance in a situation where fine, well-...