Virus-induced cochlear inflammation in newborn mice alters auditory function

Area of Science:

• Otolaryngology
• Virology
• Neuroscience

Background:

• Human cytomegalovirus (HCMV) is a leading cause of congenital sensorineural hearing loss (SNHL).
• Mechanisms underlying SNHL in congenital HCMV (cCMV) infections remain unclear.
• Murine cytomegalovirus (MCMV) models offer insights into auditory development and CMV-induced hearing impairment.

Purpose of the Study:

• To investigate the mechanisms of sensorineural hearing loss (SNHL) in a murine model of congenital cytomegalovirus (CMV) infection.
• To determine the role of cochlear inflammation and direct viral damage in auditory dysfunction.
• To assess the impact of inflammation on cochlear structures like hair cells and spiral ganglion neurons.

Main Methods:

• Utilized a murine model of MCMV infection during the critical period of auditory development.
• Assessed auditory function using auditory brainstem response (ABR) threshold measurements.
• Performed histological analyses of cochlear tissues to evaluate hair cell (HC) and spiral ganglion neuron (SGN) integrity.
• Investigated the therapeutic effect of corticosteroid treatment on cochlear inflammation and auditory function.

Main Results:

• MCMV infection led to focal cochlear inflammation and SNHL in 50%-60% of infected mice.
• Histological analysis revealed preserved hair cells but decreased spiral ganglion neurons, synapses, and neurites.
• Corticosteroid treatment reduced cochlear inflammation, preserved SGNs, and improved auditory function.
• These findings indicate inflammation, not direct viral damage, is a key factor in MCMV-induced SNHL.

Conclusions:

• Virus-induced cochlear inflammation during early auditory development contributes significantly to SNHL in congenital CMV infections.
• Damage to spiral ganglion neurons and their connections, rather than hair cell loss, is a primary pathology.
• Targeting cochlear inflammation may be a therapeutic strategy to prevent or mitigate hearing loss in infants with cCMV.