Electrical Stimulation Degenerated Cochlear Synapses Through Oxidative Stress in Neonatal Cochlear Explants

Area of Science:

• Neuroscience
• Otolaryngology
• Biomedical Engineering

Background:

• Neurostimulation devices modulate neural function using electrical stimulation (ES).
• The impact of ES on neural structures, particularly in the cochlea, remains unclear.
• Cochlear implant recipients show delayed hearing loss despite ES not affecting hair cell morphology.

Purpose of the Study:

• To investigate the effects of ES on cochlear structures in vitro.
• To elucidate the mechanisms underlying ES-induced cochlear damage.
• To explore potential protective agents against ES-induced cochlear degeneration.

Main Methods:

• Utilized a novel cochlear explant culture model with charge-balanced biphasic ES.
• Assessed hair cell quantity and morphology.
• Quantified inner hair cell (IHC) synapses and spiral ganglion neuron (SGN) peripheral fiber density.
• Investigated the role of calcium influx using voltage-dependent calcium channel (VDCC) blockers.
• Measured reactive oxygen/nitrogen species (ROS/RNS) levels.
• Examined the expression of glutathione peroxidases (GPx1, GPx2) and the effect of ebselen.

Main Results:

• ES did not alter hair cell quantity or morphology.
• ES significantly decreased IHC synapses and SGN peripheral fiber density in a dose- and time-dependent manner.
• Inhibition of calcium influx attenuated ES-induced loss of SGN fibers and IHC synapses.
• ES increased ROS/RNS, an effect abolished by calcium influx inhibition.
• ES decreased GPx1 and GPx2 levels; ebselen counteracted this and protected SGN fibers.

Conclusions:

• ES in vitro induces degeneration of SGN peripheral fibers and IHC synapses.
• Calcium influx and subsequent oxidative stress are critical mechanisms in ES-induced cochlear damage.
• Ebselen demonstrates potential as a protective agent against ES-induced cochlear synaptic degeneration.