Journal Club: Mouse model of the acute, peripheral vestibular system damage

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Today's journal article

Zhou P, Wang J, Zhang Y, Xu X, Liu C, Zhang R, Shen Y, Li F, Qu W, Huang Z, Dai C. A novel mouse model of acute vestibular dysfunction via semicircular canal injection of absolute ethanol. 

Why I picked this article

Our inner ear contains not only the hearing organ, the cochlea, but also the peripheral vestibular system. The vestibular system is responsible for our sense of balance. Damage to the peripheral vestibular system can cause vertigo, as seen in Meniere's disease. 

There are many models to study hearing loss in mice, but far fewer when it comes to vestibular dysfunction. Particularly, minimally invasive ones that don’t require major damage or sacrifice of other inner ear functions are useful. This research introduces a simpler surgical model that induces consistent vestibular dysfunction by injecting absolute ethanol into the semicircular canal.

Some of the research findings

Animal Model: 
  • adult male C57BL/6J mice (aged 12–16 weeks)
  • performed a canalostomy (surgical opening of the semicircular canal)
  • a polyimide tube with an inner diameter 0.1mm was inserted into the posterior semi-circular canal. 
  • 2 μL of absolute ethanol directly into the canal
  • after two-minutes, the tube was cut and surgical site was sealed. 

Findings:  

  • The mice showed severe vestibular symptoms soon after surgery:
    • Weight loss
    • Postural deviation
    • Reduced locomotion
    • Impaired horizontal vestibulo-ocular reflex (hVOR)
  • There was an acute vestibular syndrome observed immediately following the surgery, including head tilt and tail-hanging rotations. 
  • Auditory brainstem response showed loss of hearing in the ear treated with ethanol. 
  • Microscopy finding showed the damage to the vestibular sensory cells in the area "ampulla". Vestibular hair cells were lost in ethanol-treated ear. 
  • Static vestibular compensation (balance while still) was mostly complete within 14 days.
  • Dynamic compensation (balance during movement) recovered more gradually over time. 
A part of Figure 3B, showing happy ampulla (sensory part of the semi-circular canal) on the left and unhappy, ethanol treated ampulla on the right. Zhou et al. (2025).

Overall, ethanol caused vestibular and cochlear damage at sensory cell level. The approach is minimally invasive and reproducible.

Haruna's takeaway

I think our colleague Dr Rachael Taylor will be so excited to read this paper. There are far fewer animal models available to investigate the pathophysiology of the peripheral vestibular system. More study like this may help us understand more about the synaptic pathologies, or neuropathy in the vestibular system, for example. 

I’d be very curious to see if this model could be used for testing vestibular rehabilitation strategies by the vestibular implant, which apparently is already coming. It may also be useful for inner ear drug delivery, or even looking at central compensation mechanisms in the brain. This model may also be very powerful when combined further with other research tools like the optical coherence tomography approach (journal club from a while ago) which can be used to look at the semi-circular canals directly. 

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This is Haruna's 44/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.