Vestibular Compensation after Vestibular Dysfunction Induced by Arsanilic Acid in Mice

Abstract

When vestibular function is lost, vestibular compensation works for the reacquisition of body balance. For the study of vestibular dysfunction and vestibular compensation, surgical or chemical labyrinthectomy has been performed in various animal species. In the present study, we performed chemical labyrinthectomy using arsanilic acid in mice and investigated the time course of vestibular compensation through behavioral observations and histological studies. The surgical procedures required only paracentesis and storage of 50 µL of p-arsanilic acid sodium salt solution in the tympanic cavity for 5 min. From behavioral observations, vestibular functions were worst at 2 days and recovered by 7 days after surgery. Spontaneous nystagmus appeared at 1 day after surgery with arsanilic acid and disappeared by 2 days. Histological studies revealed specific damage to the vestibular endorgans. In the ipsilateral spinal vestibular nucleus, the medial vestibular nucleus, and the contralateral prepositus hypoglossal nucleus, a substantial number of c-Fos-immunoreactive cells appeared by 1 day after surgery with arsanilic acid, with a maximum increase in number by 2 days and complete disappearance by 7 days. Taken together, these findings indicate that chemical labyrinthectomy with arsanilic acid and the subsequent observation of vestibular compensation is a useful strategy for elucidation of the molecular mechanisms underlying vestibular pathophysiologies.

Cerebrocortical activation following unilateral labyrinthectomy in mice characterized by whole-brain clearing: implications for sensory reweighting

“…All the mice that underwent chemical UL showed ipsilesional head roll-tilt and impaired rotarod performance. Although the present study did not assess direct vestibular damages, these behavioral results were similar to those from a previous study using the same concentration of arsanilate in which peripheral vestibular organ damages were confirmed histologically 16 . The head roll-tilt peaked on day 2 and lasted up to 10 days after the UL (Fig.…”

“…Chemical UL, rather than surgical UL, was chosen because surgical UL is technically difficult to perform at the small inner ear of mice. Arsanilate was used because previous studies have reported that UL using arsanilate is a suitable model to investigate the mechanisms of vestibular compensation in mice 16 .…”

Longitudinal [18]UCB-H/[18F]FDG imaging depicts complex patterns of structural and functional neuroplasticity following bilateral vestibular loss in the rat

“…We think that functional changes of central auditory networks (e.g., cochlear nucleus, colliculus inferior) reflect some concomitant damage of toxic BL to either the cochlear hair cells or alternatively an impairment of sound conduction by damage to the tympanic membrane. Of note, in a mouse model of arsanilate-induced labyrinthectomy no significant damage was found to the hair cells of the cochlea and stria vascularis, but an elevated threshold of auditory brainstem responses due to paracentesis of the tympanic membrane was detected 45 . Damage to inner ear inputs resulted in a delayed loss of synaptic density in the same regions (vestibular nuclei, vestibular cerebellum, colliculus inferior), which slowly increased until 9 weeks post BL.…”

Live imaging and functional changes of the inner ear in an animal model of Meniere’s disease

“…( B ) Animals administered desmopressin 4 weeks after electrocauterization of the ES (n = 3). Balance disorder, such as falling down and/or circling, were scored from − 3 to 3 as follows: 0, no visible signs; 1 and − 1, slight presence of the irritative and paralytic signs; 2 and − 2, clear evidence of the irritative and paralytic signs; and 3 and − 3, the maximum expression of the irritative and paralytic signs, respectively, according to Ito et al 31 We defined irritative and paralytic balance disorders as falling down and circling to the right or left (surgical side), respectively. Each symbol represents 1 animal.…”

“…We defined irritative and paralytic balance disorders as falling down and circling to the right or left (surgical side), respectively. These behaviors were scored from − 3 to 3 as follows: 0, no visible signs; 1 and − 1, slight presence of the irritative and paralytic signs; 2 and − 2, clear evidence of the irritative and paralytic signs; and 3 and − 3, the maximum expression of the irritative and paralytic signs, respectively, according to Ito et al 31 Postural disturbances during a vestibular attack were recorded.…”