The aim of this study was to assess the effect of Vertigoheel on central vestibular compensation and cognitive deficits in rats subjected to peripheral vestibular loss. Young adult male Long Evans rats were subjected to bilateral vestibular insults through irreversible sequential ototoxic destructions of the vestibular sensory organs. Vestibular syndrome characteristics were monitored at several time points over days and weeks following the sequential insults, using a combination of behavioral assessment paradigms allowing appreciation of patterns of change in static and dynamic deficits, together with spatial navigation, learning, and memory processes. Vertigoheel administered intraperitoneally significantly improved maximum body velocity and not moving time relative to its vehicle control on days 2 and 3 and on day 2, respectively, after unilateral vestibular lesion (UVL). It also significantly improved postural control relative to its vehicle 1 day after UVL. Conversely, Vertigoheel did not display any significant effect vs. vehicle on the severity of the syndrome, nor on the time course of other examined parameters, such as distance moved, mean body velocity, meander, and rearing. Spatial cognition testing using Y- and T-maze and eight-radial arm maze did not show any statistically significant difference between Vertigoheel and vehicle groups. However, Vertigoheel potentially enhanced the speed of learning in sham animals. Evaluating Vertigoheel's effect on thigmotaxis during the open-field video tracking test revealed no significant difference between Vertigoheel and its vehicle control groups suggesting that Vertigoheel does not seem to induce sedative or anxiolytic effects that could negatively affect vestibular and memory function. Present observations reveal that Vertigoheel improves central vestibular compensation following the unilateral peripheral vestibular loss as demonstrated by improvement of specific symptoms.

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. To date, however, there is no curative solution to these pathologies and the effectiveness of treatments used to reduce symptoms in the management of patients is discussed. Thus, elucidating the biological mechanisms correlated to the expression kinetics of the vestibular syndrome is useful for the development of potential therapeutic candidates with a view to relieving patients and limiting emergency hospitalizations. Recently, a robust antivertigo effect of thyroxine (T4) was demonstrated in a rodent model of impaired vestibular function induced by unilateral surgical section of the vestibular nerve. The aim of the present study was to assess thyroid hormones L-T4 and triiodothyronine (T3) as well as the bioactive thyroid hormone metabolite TRIAC on a rodent model of acute unilateral vestibulopathy more representative of clinical vestibular pathology. To this end, a partial and transient unilateral suppression of peripheral vestibular inputs was induced by an excitotoxic lesion caused by transtympanic injection of kainic acid (TTK) into the inner ear of adult rats. Vestibular syndrome and functional recovery were studied by semi-quantitative and quantitative assessments of relevant posturo-locomotor parameters. In contrast to the effect previously demonstrated in the complete and irreversible vestibular injury model, administration of thyroxine in the TTK rodent model did not display significant antivertigo effect. However, it is noteworthy that administration of thyroxine showed trends to prevent posturo-locomotor alterations. Furthermore, the results of the current study suggested that a single dose of thyroxine is sufficient to induce the same effects on vestibular syndrome observed with sub-chronic administration, and that reducing the T4 dose may more efficiently prevent the appearance of vestibular deficits induced by the excitotoxic type lesion. Finally, comparison of the antivertigo effect of T4 in different vestibulopathy models enables us to determine the therapeutic indication in which thyroxine could be a potential therapeutic candidate.

Damage to the peripheral vestibular system is known to generate a syndrome characterized by postural, locomotor, oculomotor, perceptual and cognitive deficits. Current pharmacological therapeutic solutions for these pathologies lack specificity and efficacy. Recently, we demonstrated that apamin, a specific SK channel blocker, significantly reduced posturo-locomotor and oculomotor deficits in the cat and the rat. The aim of the present study was to test the antivertigo potential of compounds belonging to the SK antagonists family, such as Acacetin and Fluoxetine. Young rats were subjected to unilateral ototoxic lesions of the vestibular organ using transtympanic administration of arsanilic acid (TTA) to evoke unilateral vestibular loss (UVL). Vestibular syndrome was monitored using behavioural evaluation allowing appreciation of the evolution of static and dynamic posturo-locomotor deficits. A significant effect of the TTA insult was only found on the distance moved, the mean body velocity and the not moving time. From day 2 to week 2 after TTA, the distance moved and the mean body velocity were significantly decreased, while the not moving time was significantly increased. Acacetin does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine two weeks before TTA and over three weeks after TTA (preventive group) does not evoke any significant change in the vestibular posturo-locomotor parameters’ kinetics. Administration of Fluoxetine from three weeks after TTA significantly delayed the functional recovery. This study demonstrates that Acacetin or Fluoxetine in TTA vestibulo-injured rats does not bring any significant benefit on the posture and locomotor balance deficits.