Different Types of Environmental Stressors Could Have Disruptive or Constructive Effects on Vestibular Compensation

Background and Aim: Stress could play either helpful or harmful roles in vestibular compensation, the process of recovery after vestibular system lesions. Herein, we examined the effect of two stressor types on vestibular compensation: chronic anxiety disorder induced by early maternal separation (MS), and caloric restriction by an intermittent fasting (IF) diet. Methods: Male Wistar rats (n=56) received maternal separation (the MS group), intermittent fasting (IF group), unilateral vestibular deafferentation (UVD group), or a mixture of these interventions (UVD+IF, UVD+MS, and UVD+IF+MS). All the groups were compared with control animals. The animals’ balance, motor coordination, anxiety, locomotor activity, and serum cortisol levels were evaluated by rotarod, open field, and enzyme-linked immunosorbent assay methods, respectively. The data were compared with those of the healthy control (HC) group. Results: The UVD animals did not show a significant change in the time on the rod, except for the IF+UVD group (p=0.04). There was no significant difference between the experimental groups on the open field indices, except for the MS+IF+UVD group which traveled a significantly less total distance (p=0.02). Serum cortisol levels were significantly higher than HCs for all the groups except for the sham saline and IF+UVD group (p<0.05). Conclusion: IF seems to promote compensation after UVD, while MS may disrupt it. However, IF loses its beneficial outcomes if the animal has received another source of stress, i.e. MS.

Sensorimotor Rehabilitation Promotes Vestibular Compensation in a Rodent Model of Acute Peripheral Vestibulopathy by Promoting Microgliogenesis in the Deafferented Vestibular Nuclei

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 of this study was to highlight the behavioural and cellular consequences of a vestibular rehabilitation protocol adapted to a rat model of unilateral vestibular neurectomy. We developed a progressive sensory-motor rehabilitation task, and the behavioural consequences were quantified using a weight-distribution device. This analysis method provides a precise and ecological analysis of posturolocomotor vestibular deficits. At the cellular level, we focused on the analysis of plasticity mechanisms expressed in the vestibular nuclei. The results obtained show that vestibular rehabilitation induces a faster recovery of posturolocomotor deficits during vestibular compensation associated with a decrease in neurogenesis and an increase in microgliogenesis in the deafferented medial vestibular nucleus. This study reveals for the first time a part of the underlying adaptative neuroplasticity mechanisms of vestibular rehabilitation. These original data incite further investigation of the impact of rehabilitation on animal models of vestibulopathy. This new line of research should improve the management of vestibular patients.

The Cognitive-Vestibular Compensation Hypothesis: How Cognitive Impairments Might Be the Cost of Coping With Compensation

Previous research in vestibular cognition has clearly demonstrated a link between the vestibular system and several cognitive and emotional functions. However, the most coherent results supporting this link come from rodent models and healthy human participants artificial stimulation models. Human research with vestibular-damaged patients shows much more variability in the observed results, mostly because of the heterogeneity of vestibular loss (VL), and the interindividual differences in the natural vestibular compensation process. The link between the physiological consequences of VL (such as postural difficulties), and specific cognitive or emotional dysfunction is not clear yet. We suggest that a neuropsychological model, based on Kahneman’s Capacity Model of Attention, could contribute to the understanding of the vestibular compensation process, and partially explain the variability of results observed in vestibular-damaged patients. Several findings in the literature support the idea of a limited quantity of cognitive resources that can be allocated to cognitive tasks during the compensation stages. This basic mechanism of attentional limitations may lead to different compensation profiles in patients, with or without cognitive dysfunction, depending on the compensation stage. We suggest several objective and subjective measures to evaluate this cognitive-vestibular compensation hypothesis.

Effects of Galvanic Vestibular Stimulation on Vestibular Compensation in Unilaterally Labyrinthectomized Mice

Objectives: To investigate the ameliorating effects of sinusoidal galvanic vestibular stimulation (GVS) on vestibular compensation from unilateral vestibular deafferentation (UVD) using a mouse model of unilateral labyrinthectomy (UL).Methods: Sixteen male C57BL/6 mice were allocated into two groups that comprise UL groups with GVS (GVS group, n = 9) and without GVS intervention (non-GVS group, n = 7). In the experimental groups, we assessed vestibulo-ocular reflex (VOR) recovery before (baseline) and at 3, 7, and 14 days after surgical unilateral labyrinthectomy. In the GVS group, stimulation was applied for 30 min daily from postoperative days (PODs) 0–4 via electrodes inserted subcutaneously next to both bony labyrinths.Results: Locomotion and VOR were significantly impaired in the non-GVS group compared to baseline. The mean VOR gain of the non-GVS group was attenuated to 0.23 at POD 3 and recovered continuously to the value of 0.54 at POD 14, but did not reach the baseline values at any frequency. GVS intervention significantly accelerated recovery of locomotion, as assessed by the amount of circling and total path length in the open field tasks compared to the non-GVS groups on PODs 3 (p &lt; 0.001 in both amount of circling and total path length) and 7 (p &lt; 0.01 in amount of circling and p &lt; 0.001 in total path length, Mann–Whitney U-test). GVS also significantly improved VOR gain compared to the non-GVS groups at PODs 3 (p &lt; 0.001), 7 (p &lt; 0.001), and 14 (p &lt; 0.001, independent t-tests) during sinusoidal rotations. In addition, the recovery of the phase responses and asymmetry of the VOR was significantly better in the GVS group than in the non-GVS group until 2 weeks after UVD (phase, p = 0.001; symmetry, p &lt; 0.001 at POD 14).Conclusion: Recoveries for UVD-induced locomotion and VOR deficits were accelerated by an early intervention with GVS, which implies that GVS has the potential to improve vestibular compensation in patients with acute unilateral vestibular failure.

Breaking a dogma: acute anti-inflammatory treatment alters both post-lesional functional recovery and endogenous adaptive plasticity mechanisms in a rodent model of acute peripheral vestibulopathy

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 spinning vertigo, spontaneous ocular nystagmus and oscillopsia, perceptual-cognitive, posturo-locomotor, and vegetative disorders. We assessed the effectiveness of acute corticotherapy, and the functional role of acute inflammation observed after sudden unilateral vestibular loss. Methods We used the rodent model of unilateral vestibular neurectomy, mimicking the syndrome observed in patients with APV. We treated the animals during the acute phase of the vestibular syndrome, either with placebo or methylprednisolone, an anti-inflammatory corticosteroid. At the cellular level, impacts of methylprednisolone on endogenous plasticity mechanisms were assessed through analysis of cell proliferation and survival, glial reactions, neuron’s membrane excitability, and stress marker. At the behavioral level, vestibular and posturo-locomotor functions’ recovery were assessed with appropriate qualitative and quantitative evaluations. Results We observed that acute treatment with methylprednisolone significantly decreases glial reactions, cell proliferation and survival. In addition, stress and excitability markers were significantly impacted by the treatment. Besides, vestibular syndrome’s intensity was enhanced, and vestibular compensation delayed under acute methylprednisolone treatment. Conclusions We show here, for the first time, that acute anti-inflammatory treatment alters the expression of the adaptive plasticity mechanisms in the deafferented vestibular nuclei and generates enhanced and prolonged vestibular and postural deficits. These results strongly suggest a beneficial role for acute endogenous neuroinflammation in vestibular compensation. They open the way to a change in dogma for the treatment and therapeutic management of vestibular patients.

Vestibular neuronitis

Vestibular neuronitis occurs as a result of damage to the vestibular nerve and is manifested by a sudden and prolonged attack of vestibular vertigo, accompanied by nausea, vomiting and imbalance. Questions of etiology, pathogenesis, clinical picture, diagnosis and treatment of VN are discussed. The disease is associated with selective inflammation (viral or infectious-allergic genesis) of the vestibular nerve. The role of herpes simplex virus type 1 is confirmed by cases of herpetic encephalitis in VN. In 2020, cases of VN development in patients with COVID-19 are described. VN usually affects the upper branch of the vestibular nerve, which innervates the horizontal and anterior semicircular canals. The duration of vertigo with VN ranges from several hours to several days. The timing of the restoration of vestibular function depends on the degree of damage to the vestibular nerve, the speed of central vestibular compensation and the patient’s performance of vestibular gymnastics. Some patients, months and even years after VN, experience significant instability. The diagnosis of VL is based on the clinical picture of the disease, the results of an otoneurological examination, and the exclusion of other diseases. VN treatment is aimed at reducing dizziness, nausea and vomiting and accelerating vestibular compensation. In our country VN is rarely diagnosed, which is associated with poor awareness of doctors about this disease. The article presents the observation of a 46-year-old patient with VN, who was mistakenly diagnosed with vertebrobasilar insufficiency, which contributed to the patient’s long-term disability. Establishing the correct diagnosis, educational work with the patient, conducting vestibular gymnastics led to an improvement in the condition, regression of instability. The issues of the effectiveness of vestibular gymnastics, the use of betahistine to accelerate the recovery of patients with VN are discussed.

L-Thyroxine improves vestibular compensation in a rat model of acute peripheral vestibulopathy

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-T4 treatment reduced the vestibular syndrome and significantly promoted vestibular compensation. Thyroid hormone receptors (TRα and TRβ) and type II iodothyronine deiodinase (DIO2) were present in the vestibular nuclei (VN), supporting a local action of L-T4. We confirmed the T4-induced metabolic effects by demonstrating an increase in the number of cytochrome oxidase-labelled neurons in the VN three days after the lesion. L-T4 treatment modulated glial reaction by decreasing both microglia and oligodendrocytes in the deafferented VN three days after UVN and increased cell proliferation. The survival of newly generated cells was not affected, but neuronal differentiation was altered by the L-T4 treatment.