losartan-potassium and Hearing-Loss--Sensorineural

The aim of the present study was to evaluate the expression of erythropoietin (Epo) and the Epo receptor (Epo‑R) in the spiral ganglion neurons (SGNs) of the rat inner ear, and to assess the effect of Epo adenovirus vector (Ad‑Epo) on the spontaneous apoptosis of SGNs. A total of 60 ears from 30 healthy neonatal (2‑3 days postnatal) Sprague‑Dawley rats were used to examine the expression of Epo in the SGNs. The rats were divided into three groups: The negative control group, the vector control group [infected with a green fluorescent protein expression vector (Ad‑GFP)] and the Ad‑Epo group (infected with Ad‑Epo). The expression of Epo and Epo‑R was detected by immunohistochemistry and dual immunofluorescence staining using polyclonal antibodies directed against Epo and Epo‑R, followed by confocal laser‑scanning microscopy. An adenovirus vector was constructed and used to transfect the cultured SGNs. Following adenovirus infection, apoptosis of the SGNs was evaluated and Epo protein expression was assessed. Epo and Epo‑R were widely expressed in the plasma membrane and the cytoplasm of the SGNs, as well as in the organ of Corti and the stria vascularis within the inner ear. Epo protein expression was upregulated in the Ad‑Epo group compared with that in the other two groups (P<0.05). Apoptotic cells were seldom observed at day 4 of SGN culture in the negative control group. At day 7, marked apoptotic cells were detected in the negative control group and the vector control group. The apoptosis level in the Ad‑Epo group was significantly decreased compared with that in the negative control group or the vector control group at day 7 (P<0.05). In conclusion, Epo and Epo‑R are expressed in the SGNs of the inner ear of the rat, and Ad‑Epo can decrease the spontaneous apoptosis of SGNs, which may provide a basis for the prevention or alleviation of sensorineural hearing loss.

Topics: Adenoviridae; Animals; Apoptosis; Cells, Cultured; Ear, Inner; Erythropoietin; Gene Expression; Genetic Therapy; Genetic Vectors; Hearing Loss, Sensorineural; Neurons; Rats, Sprague-Dawley; Receptors, Erythropoietin; Transfection

The Cdh23(erl/erl) mice are a novel mouse model for DFNB12 and are characterized by progressive hearing loss. In this study, erythropoietin (EPO) was given to the Cdh23(erl/erl) mice by intraperitoneal injection every other day from P7 for 7 weeks. Phosphate-buffered saline-treated or untreated Cdh23(erl/erl) mice were used as controls. Auditory-evoked brainstem response (ABR) thresholds and distortion product oto-acoustic emission (DPOAE) were measured in the mouse groups at the age of 4, 6 and 8 weeks. The results show that EPO can significantly decrease the ABR thresholds in the Cdh23(erl/erl) mice as compared with those of the untreated mice at stimulus frequencies of click, 8-, 16- and 32-kHz at three time points. Meanwhile, DPOAE amplitudes in the EPO-treated Cdh23(erl/erl) mouse group were significantly higher than those of the untreated groups at f2 frequency of 15383 Hz at the three time points. Furthermore, the mean percentage of outer hair cell loss at middle through basal turns of cochleae was significantly lower in EPO-treated Cdh23(erl/erl) mice than in the untreated mice (P<0.05). This is the first report that EPO acts as an otoprotectant in a DFNB12 mouse model with progressive hearing loss.

Topics: 3,4-Dihydroxyphenylacetic Acid; Acoustic Stimulation; Analysis of Variance; Animals; Auditory Threshold; Cadherins; Cell Count; Chi-Square Distribution; Cochlea; Disease Models, Animal; Erythropoietin; Evoked Potentials, Auditory, Brain Stem; Hair Cells, Auditory; Hearing Loss, Sensorineural; Mice; Mice, Transgenic; Mutation; Otoacoustic Emissions, Spontaneous; Time Factors