The mechanisms of the response in the murine cochlear lateral wall following sensorineural hearing loss (SNHL) are poorly understood. We focused on comparing the endocochlear potential (EP) with morphological changes in the lateral wall and expression of four important potassium (K(+)) transporters in a mouse model of SNHL induced by co-administration of aminoglycoside and loop diuretic. The expression of the α1 and α2 isoforms of Na,K-ATPase, Na-K-2Cl-Cotransporter-1 (NKCC1) and potassium channel KCNQ1 was assessed. The EP showed a significant decline at 12h post-treatment followed by complete recovery by 2 days post-treatment. The EP was maintained at near normal levels in animals deafened for periods up to 112 days. Despite this recovery, there was a significant and progressive decrease in the thickness of the stria vascularis, which was predominantly due to atrophy of marginal cells. Both protein and mRNA expression of α1 and α2 isoforms of Na,K-ATPase and NKCC1 in the lateral wall were dramatically reduced following a long-term deafening. KCNQ1 expression remained unchanged. These observations provide insight into the detailed mechanisms of EP modulation following SNHL and may have crucial implications in the future treatment of aminoglycoside-induced hearing loss.
"d Schmiedt , 1992 ) . Morphological changes in the stria may also be associated with treatment by drugs and noise but may not be causal to hearing loss . Strial pathology can be observed after aminoglycoside challenge ( Forge et al . , 1987 ) , but the endocochlear potential remains stable until late in ototoxic treatment ( Komune et al . , 1987 ; Xiong et al . , 2011 ) , negating a functional consequence of such alterations . Cisplatin may affect both strial morphology and function ( Laurell et al . , 2007 ) but at least some of these changes are reversible ( Klis et al . , 2000 ) and therefore not a direct cause of hair cell loss . The effects of noise on lateral wall tissues are variable , probabl"
[Show abstract][Hide abstract] ABSTRACT: Understanding underlying pathological mechanisms is prerequisite for a sensible design of protective therapies against hearing loss. The triad of age-related, noise-generated, and drug-induced hearing loss displays intriguing similarities in some cellular responses of cochlear sensory cells such as a potential involvement of reactive oxygen species (ROS) and apoptotic and necrotic cell death. On the other hand, detailed studies have revealed that molecular pathways are considerably complex and, importantly, it has become clear that pharmacological protection successful against one form of hearing loss will not necessarily protect against another. This review will summarize pathological and pathophysiological features of age-related hearing impairment (ARHI) in human and animal models and address selected aspects of the commonality (or lack thereof) of cellular responses in ARHI to drugs and noise.
[Show abstract][Hide abstract] ABSTRACT: To compare safety, reliability and usefulness of two deafening protocols on animal mouse model, based on aminoglycosides exposure
Adults mice, Bulb/C, deafened with kanamycine 14 days treatment (group I), single kanamycin injection followed by etacrinic acid administration (group II) and control group. Hearing evaluation performed with ABR recordings on 6th day after drug exposure
Both protocols were not able to guarantee complete ablation of the inner ear in tested animals. Although short deafening strategy was more effective (83.33% deaf mice) it was combined with high rate of mortality during general anesthesia for hearing evaluation.
Variable outcomes in deafening mouse animal model implies the necessity of hearing evaluation every time prior to the pathophysiological as well as molecular studies. Mice exposed to severe oto- and nephrotoxic insult do not recover after anesthetic drug administration, thus harvesting inner ear tissues especially as the source of RNA should be performed immediately after ABR recordings.
Otolaryngologia polska. The Polish otolaryngology 02/2012; 66(1):56-60. DOI:10.1016/S0030-6657(12)70751-5
[Show abstract][Hide abstract] ABSTRACT: Age-related hearing loss (ARHL) is the most common human morbidity. However, the molecular mechanisms underlying ARHL are little known. In the present study, the expression of Cav1.3 calcium channels in the C57BL/6J ARHL mouse cochlea was investigated. The hearing threshold was assessed by auditory brainstem response and the expressions of Cav1.3 calcium channels at the protein and mRNA levels were detected by immunohistochemistry, western blot, and real-time RT-PCR. Associated with the auditory brainstem response threshold increased with age, the Cav1.3 expression was gradually decreased. In comparison with 4-week-old mice, Cav1.3 expressions in the cochlea at 14, 24, and 48 weeks of age were significantly and gradually decreased at both the protein and the mRNA levels. Immunohistochemistry showed that the expression of Cav1.3 was apparently reduced at the inner hair cells, outer hair cells, and stria vascularis in the cochlear lateral wall in the aged mice. Our findings indicate that Cav1.3 calcium channel expression in the cochlea is reduced in the ARHL mice and is associated with ARHL. The data also support a view that Cav1.3 calcium channel is a good target for prevention and therapy of ARHL.
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