Effects of Therapeutic Hypothermia on Macrophages in Mouse Cochlea Explants

Abstract

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.

Targeted therapeutic hypothermia protects against noise induced hearing loss

“…Although these studies showed benefits of MTH, systemic application can result in unintended complications and is simply not feasible as a therapeutic application for a global population. Recent studies in cochlear implant trauma ( Tamames et al, 2016 ; Bader et al, 2023 ; Schmutzhard et al, 2023 ) and cisplatin injury ( Spankovich et al, 2016 ; Stanford et al, 2020 ) models provide evidence for localized MTH providing cochlear neuroprotection. Furthermore, several approaches have been proposed to achieve therapeutic levels of hypothermia ( Spankovich et al, 2016 ; Tamames et al, 2016 , 2018 ; Bader et al, 2020 ; Stanford et al, 2020 ; Arteaga et al, 2023 ).…”