Journal Club: Radiation-induced sensorineural hearing loss: animal models show increase in cochlear macrophages

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Today's journal article

Gao Y, Chen G, Wang J, Cai Z, Pang J, Zheng Y. Distribution of macrophages in the cochlea following radiation-induced sensorineural hearing loss. 

  • Cell Signal. 2025 Oct;134:111958. 
  • doi: 10.1016/j.cellsig.2025.111958. 
  • Epub 2025 Jun 20. PMID: 40545115.
  • Available online at: https://www.sciencedirect.com/science/article/pii/S0898656825003730

Why I picked this article

This study contributes to the understanding of how radiation-induced sensorineural hearing loss develops. 

Authors refer to Strojan et al (2017) https://doi.org/10.1016/j.ctrv.2017.07.003   that following radiation therapy of head and neck tumours, hearing loss is the 2nd most common complication, with the incidence of sensorineural hearing loss being ~43%. This is a very staggering %. While the primary focus of radiation therapy is recovery from cancer being treated, the loss of hearing will impact the patients' quality of life after recovery. 

To understand how hearing loss develops following radiation, this research hypothesised the involvement of macrophages in the process. If how hearing loss develops following radiotherapy is better understood, then there may be an opportunity to supplement the radiation therapy with an additional drug to reduce the chance of sensorineural hearing loss. 

Some of the research findings

Animal model:

  • Male mouse (C57BL/6), 6-week-old adult mice were used. 
  • Irradiation group mice received a single 15 Gy dose of localised irradiation (this is when they were 6-week-old. 
  • (15 Gy (grey) is, according to my quick Google search, a common dose for treating some cancers, such as prostate cancer.)
  • In this study, a custom-fitted lead plate was used to protect other organs (other than the cochlea) from radiation. This was presumably important to avoid any systemic effect of radiation. 
  • Microscopy was used to assess the cochlea and count macrophages: 
    • anti-Iba1 (Abcam, ab153696, 1:100) = macrophage marker
    • anti-βIII Tubulin (Abcam, ab18207, 1:200) = auditory neuron marker 
    • ADAM17 polyclonal antibody (Signalway Antibody, 29,051–2, 1:100) = target protein they found to be increased by radiation in this study.
A part of Figure 3b, Gao et al. (2025). Red colour is the macrophage in the cochlea. See publication for details. 

Finding:

  • Radiation increased macrophage number in the cochlea, 12 - 20 weeks after radiation. 
  • Macrophage increase was seen in all areas researched, such as where you find auditory neurons, or areas with cochlear blood vessels. 
  • Sensory hair cell loss was prominent in the radiation group compared to the control, 12-20 weeks after radiation. 
  • Very nice microscopy images are presented in this publication, showing the shape of macrophages and how many macrophages are along the small blood vessels in the cochlea. They note that in the radiated animal, cochlear macrophages had a more irregular shape compared to the control. 
  • Broad screening of what kind of proteins are increased in the cochlea of irradiated animals found a protein called Adam 17 to be increased.
Overall, this study suggests that macrophage increase was observed after radiation in a delayed fashion (12 weeks onwards). 

Haruna's takeaway

The relationship between ADAM17 and macrophage or pathology of sensorineural hearing loss following radiation is still unclear. But the timeframe of macrophage increase in the cochlea following radiation seems very slow, and very interesting. Macrophage increase may be secondary to some earlier invisible acute changes in the cochlea caused by radiation. 

I find the focus on the radiation-induced sensorineural hearing loss to be interesting. Like cisplatin-induced sensorineural hearing loss, this is hearing loss secondary to medical treatment. The patient is identified prior to developing hearing loss, so there is plenty of intervention window, if we can develop drug-based therapies or other interventions to reduce the chance of developing sensorineural hearing loss after radiation therapy. Clearly, this must not interfere with the therapeutic efficacy of the radiation therapy itself. If macrophage or other inflammatory responses are shown to be the underlying mechanism of radiation-induced sensorineural hearing loss, it may be feasible to develop therapy to prevent sensorineural hearing loss in these patients. 

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This is Haruna's 13/100 of the 100-day challenge to post a science blog article every day! I love inner ear biology & cochlear physiology.