Bringuier Claire M, Hatat Bérenice, Boularand Romain, Chabbert Christian, Tighilet Brahim
Vertidiag, Montpellier, France.
Aix Marseille Université-CNRS, Laboratoire de Neurosciences Cognitives, LNC UMR 7291, Marseille, France.
Front Neurol. 2022 May 25;13:877319. doi: 10.3389/fneur.2022.877319. eCollection 2022.
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.
前庭功能受损会引发诸如姿势失衡、运动障碍、前庭眼反射改变等致残症状，还会导致空间定向障碍等认知功能受损以及自主神经功能缺陷。这些症状会在梅尼埃病或神经炎患者中突然发作，可能导致紧急住院治疗。然而，迄今为止，针对这些病症尚无治愈方法，且用于减轻患者症状的治疗方法的有效性仍存在争议。因此，阐明与前庭综合征表达动力学相关的生物学机制，对于开发潜在的治疗候选药物以缓解患者症状并减少紧急住院治疗具有重要意义。最近，在单侧前庭神经手术切断诱导的前庭功能受损的啮齿动物模型中，证实了甲状腺素（T4）具有强大的抗眩晕作用。本研究的目的是在更具临床前庭病理学代表性的急性单侧前庭病变啮齿动物模型中，评估甲状腺激素L-T4、三碘甲状腺原氨酸（T3）以及生物活性甲状腺激素代谢产物TRIAC。为此，通过向成年大鼠内耳经鼓膜注射 kainic 酸（TTK）引发兴奋性毒性损伤，诱导外周前庭输入的部分和短暂单侧抑制。通过对相关姿势运动参数的半定量和定量评估，研究前庭综合征和功能恢复情况。与先前在完全不可逆前庭损伤模型中所证实的效果不同，在TTK啮齿动物模型中给予甲状腺素并未显示出显著的抗眩晕作用。然而，值得注意的是，给予甲状腺素显示出预防姿势运动改变的趋势。此外，当前研究结果表明，单剂量甲状腺素足以诱导出与亚慢性给药观察到的对前庭综合征相同的效果，并且降低T4剂量可能更有效地预防兴奋性毒性损伤诱导的前庭缺陷的出现。最后，比较T4在不同前庭病变模型中的抗眩晕作用，使我们能够确定甲状腺素可能成为潜在治疗候选药物的治疗适应症。
