RAT COCHLEA CONTINUES TO DEVELOP AFTER BIRTH

Introduction: The ear, originates from the ectoderm, exhibits a complex structure that differs from species to species in terms of development. Objectives: This study was conducted to describe the prenatal and postnatal development process of the organ of Corti in the iner ear using light microscopy. Methods: In this study, Wistar Albino rats were used. The rats were divided into two groups as prenatal and postnatal groups. Prenatal groups consisting of embryos on day 17, 19, 21 and postnatal groups consisting of pups on days 1, 5, 10 and 15. The rats were sacrificed to investigate the cochleas by light microscopy. Results: The lumen of the cochlear tunnel was lined with pseudostratified columnar epithelia throughout the prenatal period. The cochlear tunnel was not divided into scala media, scala tympani and scala vestibuli in the embryonic sections. Organ of corti hasn’t taken its final form until postnatal day 15. Conclusion: In rats, formation of organ of Corti is completed in postnatal 15 day. Pups of rats are not able to hear in the embronic and early postnatal life.

FBXO3 Downregulation Attenuates Noise-induced Hearing Loss by Suppressing ATG10 Degradation and Activating Autophagy

Noise induced hearing loss (NIHL) is a kind of hearing impairment, which is next to the age-related hearing loss. More and more evidences have verified that overproduction of reactive oxygen species is a common pathologic phenomenon of different inner ear injury including NIHL, and autophagy contributes to attenuate NIHL by reducing oxidative stress. However, the underlying mechanism by which noise exposure causes autophagy activation remains unclear. In this study, we found that NIHL was accompanied by autophagy in the rat cochlea. Furthermore, twelve common genes were found at the GEO datasets GSE85290 and GSE8342, and E3 ubiquitination ligase FBXO3 was confirmed significantly reduced in NIHL rat cochlea. Next, we demonstrated that FBXO3 can directly binding with autophagy-related protein 10 (ATG10), which is necessary for the initiation of autophagy, and mediate its degradation. In vivo animal model treatment with rapamycin, an autophagy activator, significantly reduced the NIHL. Based on these data, we confirmed that FBXO3 played an important role in autophagy caused by NIHL, may be a potential target of NIHL treatment.

Biocompatibility of Bone Marrow-Derived Mesenchymal Stem Cells in the Rat Inner Ear following Trans-Tympanic Administration

Recent advancements in stem cell therapy have led to an increased interest within the auditory community in exploring the potential of mesenchymal stem cells (MSCs) in the treatment of inner ear disorders. However, the biocompatibility of MSCs with the inner ear, especially when delivered non-surgically and in the immunocompetent cochlea, is not completely understood. In this study, we determined the effect of intratympanic administration of rodent bone marrow MSCs (BM-MSCs) on the inner ear in an immunocompetent rat model. The administration of MSCs did not lead to the generation of any oxidative stress in the rat inner ear. There was no significant production of proinflammatory cytokines, tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6 and IL-12, due to BM-MSCs administration into the rat cochlea. BM-MSCs do not activate caspase 3 pathway, which plays a central role in sensory cell damage. Additionally, transferase dUTP nick end labeling (TUNEL) staining determined that there was no significant cell death associated with the administration of BM-MSCs. The results of the present study suggest that trans-tympanic administration of BM-MSCs does not result in oxidative stress or inflammatory response in the immunocompetent rat cochlea.

Inhibition of the Adenosine A2A Receptor Mitigates Excitotoxic Injury in Organotypic Tissue Cultures of the Rat Cochlea

The primary loss of cochlear glutamatergic afferent nerve synapses due to noise or ageing (cochlear neuropathy) often presents as difficulties in speech discrimination in noisy conditions (hidden hearing loss (HHL)). Currently, there is no treatment for this condition. Our previous studies in mice with genetic deletion of the adenosine A2A receptor (A2AR) have demonstrated better preservation of cochlear afferent synapses and spiral ganglion neurons after noise exposure compared to wildtype mice. This has informed our current targeted approach to cochlear neuroprotection based on pharmacological inhibition of the A2AR. Here, we have used organotypic tissue culture of the Wistar rat cochlea at postnatal day 6 (P6) to model excitotoxic injury induced by N-methyl-d-aspartate (NMDA)/kainic acid (NK) treatment for 2 h. The excitotoxic injury was characterised by a reduction in the density of neural processes immediately after NK treatment and loss of afferent synapses in the presence of intact sensory hair cells. The administration of istradefylline (a clinically approved A2AR antagonist) reduced deafferentation of inner hair cells and improved the survival of afferent synapses after excitotoxic injury. This study thus provides evidence that A2AR inhibition promotes cochlear recovery from excitotoxic injury, and may have implications for the treatment of cochlear neuropathy and prevention of HHL.