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OBJECTIVES. The goal of the study was to determine whether reactive oxygen species (ROS) mediates cytomegalovirus (CMV)–induced labyrinthitis. STUDY DESIGN. Murine model of CMV infection. SETTING. University of Utah laboratory. SUBJECTS AND METHODS. Nrf2 knockout mice were inoculated with murine CMV. Auditory brainstem response (ABR) and distortion product otoacoustic emissions (DPOAEs) were then performed on these and uninfected controls. BALB/c mice were inoculated with murine CMV to determine whether a marker for ROS production, dihydroethidium (DHE), is expressed 7 days after inoculation. Finally, 2 antioxidants—D-methionine and ACE-Mg (vitamins A, C, and E with magnesium)—were administered 1 hour before and after infection in inoculated mice for 14 days. Temporal bones were harvested at postnatal day 10 for DHE detection. ABR and DPOAE testing was done at postnatal day 30. Scanning electron microscopy was also performed at postnatal day 30 to evaluate outer hair cell integrity. RESULTS. Nrf2-infected mice had worse hearing than uninfected mice (P < .001). A statistically significant increase in DHE fluorescence was detected in BALB/c-infected mice as compared with uninfected mice 7 days after inoculation. D-methionine- and ACE-Mg-treated mice demonstrated an attenuation of the DHE fluorescence and a significant improvement in ABR and DPOAE thresholds when compared with untreated infected controls (P

OBJECTIVE To determine whether ganciclovir (GCV) treatment reduces sensorineural hearing loss in cytomegalovirus (CMV)-infected mice. The effects of GCV on viral load, absolute neutrophil count (ANC), and outer hair cell (OHC) integrity were also investigated. METHODS Infected BALB/c mice were inoculated with murine CMV on postnatal day 3. Those treated with GCV received an intraperitoneal injection twice a day for 14 days. Auditory thresholds were assessed using distortion product otoacoustic emission (DPOAE) and auditory brainstem response (ABR) testing 4 weeks after inoculation. Temporal bones were used for determination of viral load by quantitative polymerase chain reaction and hair cell quantification by scanning electron microscopy. ANCs were completed by an automated hematology analyzer, with manual review for confirmation. RESULTS GCV-treated CMV-infected mice had lower ABR (P

OBJECTIVES: Determine whether a murine model of cytomegalovirus (CMV) and CMV- infected children show evidence of synaptopathy. STUDY DESIGN: Murine model of CMV infection and case series SUBJECTS AND METHODS: C57 BL/6 mice were inoculated with murine-CMV (mCMV). Auditory function was assessed using Auditory Brainstem Response (ABR) and distortion product otoacoustic emission (DPOAE) testing. Temporal bones from mCMV-infected mice were used for both ribbon synapse and hair cell quantification. Four groups of children (non-CMV normal hearing, non-CMV hearing impaired, CMV normal hearing and CMV hearing impaired) underwent ABRs between 2014-2018. The outcomes included raw amplitude, wave I:V amplitude ratio, absolute latency, and interpeak latency. RESULTS: Mice at 8 weeks post mCMV infection had higher ABR and DPOAE (P < 0.05) thresholds and increased outer hair cell loss compared to uninfected mice and mCMV-infected mice at 4- and 6-weeks post infection, indicating progressive hearing loss. A reduction in the wave I amplitude and synaptic counts were noted earlier at 4 weeks in CMV-infected mice (P < 0.05). The human data indicated that the wave I:V amplitude ratio was lower on average in CMV-infected groups when compared to the uninfected cohorts. The wave I:V amplitude ratio for the click and 4k stimuli were not significantly different between the congenital CMV-infected and uninfected children with normal or with hearing loss. CONCLUSION: This study suggests mCMV infection results in a synaptopathy before hair cell damage. Additional studies need to be performed to determine whether this effect is also observed in CMV-infected children. LEVEL OF EVIDENCE: animal studies and basic science- NA; human studies: level 4.