Mild therapeutic hypothermia protects against inflammatory and proapoptotic processes in the rat model of cochlear implant trauma

Sangaletti, Rachele; Tamames, Ilmar; Yahn, Stephanie L.; Choi, James S.; Lee, Duncan; King, Curtis; Rajguru, Suhrud M.

doi:10.1016/j.heares.2022.108680

Cited by 7 publications

(4 citation statements)

References 123 publications

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“…CD163 is a selective monocyte marker and can be induced by anti-inflammatory stimuli, such as glucocorticosteroids. A similar effect can be expected with the application of hypothermia, another postulated anti-inflammatory stimulus [28][29][30]. With the selection of the CD45 marker, the analysis has been extended to the dendritic cells, another important line of immune cells.…”

Section: Introductionmentioning

confidence: 69%

Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants

Bader

Steinacher

Fischer

et al. 2023

IJMS

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Globally, over the next few decades, more than 2.5 billion people will suffer from hearing impairment, including profound hearing loss, and millions could potentially benefit from a cochlea implant. To date, several studies have focused on tissue trauma caused by cochlea implantation. The direct immune reaction in the inner ear after an implantation has not been well studied. Recently, therapeutic hypothermia has been found to positively influence the inflammatory reaction caused by electrode insertion trauma. The present study aimed to evaluate the hypothermic effect on the structure, numbers, function and reactivity of macrophages and microglial cells. Therefore, the distribution and activated forms of macrophages in the cochlea were evaluated in an electrode insertion trauma cochlea culture model in normothermic and mild hypothermic conditions. In 10-day-old mouse cochleae, artificial electrode insertion trauma was inflicted, and then they were cultured for 24 h at 37 °C and 32 °C. The influence of mild hypothermia on macrophages was evaluated using immunostaining of cryosections using antibodies against IBA1, F4/80, CD45 and CD163. A clear influence of mild hypothermia on the distribution of activated and non-activated forms of macrophages and monocytes in the inner ear was observed. Furthermore, these cells were located in the mesenchymal tissue in and around the cochlea, and the activated forms were found in and around the spiral ganglion tissue at 37 °C. Our findings suggest that mild hypothermic treatment has a beneficial effect on immune system activation after electrode insertion trauma.

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Section: Introductionmentioning

confidence: 69%

Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants

Bader

Steinacher

Fischer

et al. 2023

IJMS

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“…A previous study utilizing a mechanical cochlear implant trauma model observed that localized hypothermic induction protects against HC loss ( Tamames et al, 2016 ). As a global modulator of multiple cellular and subcellular processes, temperature management may provide wide-ranging protection targeting apoptotic mechanisms that may result in HC death and glutamate excitotoxicity that can damage synaptic ribbon integrity ( Sangaletti et al, 2022 ). Hair cell death following intense acoustic trauma may occur through several metabolic processes, with OHCs long considered to have increased vulnerability to acoustic overexposure.…”

Section: Discussionmentioning

confidence: 99%

Targeted therapeutic hypothermia protects against noise induced hearing loss

Rincon Sabatino,

Rivero,

Sangaletti

et al. 2024

Front. Neurosci.

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IntroductionExposure to occupational or recreational loud noise activates multiple biological regulatory circuits and damages the cochlea, causing permanent changes in hearing sensitivity. Currently, no effective clinical therapy is available for the treatment or mitigation of noise-induced hearing loss (NIHL). Here, we describe an application of localized and non-invasive therapeutic hypothermia and targeted temperature management of the inner ear to prevent NIHL.MethodsWe developed a custom-designed cooling neck collar to reduce the temperature of the inner ear by 3–4°C post-injury to deliver mild therapeutic hypothermia.ResultsThis localized and non-invasive therapeutic hypothermia successfully mitigated NIHL in rats. Our results show that mild hypothermia can be applied quickly and safely to the inner ear following noise exposure. We show that localized hypothermia after NIHL preserves residual hearing and rescues noise-induced synaptopathy over a period of months.DiscussionThis study establishes a minimally-invasive therapeutic paradigm with a high potential for rapid translation to the clinic for long-term preservation of hearing health.

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“…Achieving therapeutic ranges of MTH is an effective and simple way to provide protection following implantation, trauma, or iatrogenic hearing loss. Secondary injury pathways are mitigated by MTH via the modulation of inflammatory and immune responses, as well as neurotransmitter and excitatory pathways [13]. The Joint Commissions and ANSI standard range for operating room temperature is between approximately 68 and 75°C (20-24°C) [14].…”

Section: Discussionmentioning

confidence: 99%

Achieving Cochlear Therapeutic Hypothermia through Irrigation of the Mastoid and Tympanic Cavities

Beatrous,

Arteaga,

Mckee

et al. 2024

Audiol Neurotol

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Introduction: Mild therapeutic hypothermia (MTH) is an exciting nonpharmaceutical otoprotection strategy. In this study, we applied simple irrigation of the tympanic and mastoid cavities to understand the timing of both achieving MTH and recovery back to euthermic temperatures for application in the clinical setting. Methods: Three human temporal bones were used in this study in the temporal bone laboratory. A standard mastoidectomy was performed on each followed by the insertion of temperature probes into the basal turn of the cochlea via a middle cranial fossa approach. The temporal bones were warmed in heated bead baths to 37°C. The tympanic and mastoid cavities were then irrigated with room temperature water, and intracochlear temperature readings were recorded every minute. After 15 min, irrigation was stopped, and temperature readings were collected until temporal bones returned to euthermic levels. Results: Intracochlear MTH was achieved within the first minute of irrigating the tympanic and mastoid cavities. Intracochlear temperatures plateaued after 5 min around 30°C. Discontinuation of irrigation resulted in the temperature rising logarithmically above the MTH levels after 9–10 min. Conclusion: Intracochlear MTH can be achieved via irrigation of the tympanic and mastoid cavities with room temperature irrigation within 60 s. After irrigation for 5 min, hypothermic temperatures will remain therapeutic for 10 min following cessation of irrigation.

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Mild therapeutic hypothermia protects against inflammatory and proapoptotic processes in the rat model of cochlear implant trauma

Cited by 7 publications

References 123 publications

Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants

Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants

Targeted therapeutic hypothermia protects against noise induced hearing loss

Achieving Cochlear Therapeutic Hypothermia through Irrigation of the Mastoid and Tympanic Cavities

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