Delayed electrical stimulation and BDNF application following induced deafness in rats

Area of Science:

• Neuroscience
• Otolaryngology
• Regenerative Medicine

Background:

• Sensorineural hearing loss is often associated with the degeneration of spiral ganglion neurons (SGNs).
• Current treatments for hearing loss have limitations, necessitating novel therapeutic strategies.
• Protecting SGNs is crucial for preserving auditory function and cochlear implant efficacy.

Purpose of the Study:

• To investigate the efficacy of delayed, combined intracochlear electrical stimulation (ES) and brain-derived neurotrophic factor (BDNF) delivery in preventing SGN degeneration.
• To determine the impact of this combined therapy on auditory sensitivity following induced deafness in rats.
• To explore the relationship between SGN survival, peripheral process integrity, and auditory function.

Main Methods:

• Rats were subjected to gentamicin+furosemide-induced deafness.
• 30 days post-deafening, intracochlear electrodes and drug-delivery systems were implanted.
• Continuous administration of BDNF or artificial perilymph (AP) was combined with or without ES for 28 days.
• Electrically evoked auditory brainstem responses (EABRs) and SGN/peripheral process density were assessed.

Main Results:

• Combined ES and BDNF treatment significantly improved EABR thresholds compared to control groups.
• Both ES and BDNF individually enhanced SGN and peripheral process survival.
• The combination of ES and BDNF demonstrated a synergistic protective effect, outperforming individual treatments.
• A functional relationship was established between EABR thresholds and SGN/peripheral process density.

Conclusions:

• Delayed, chronic intracochlear ES and continuous BDNF administration promote SGN survival and enhance auditory sensitivity in a rat model of deafness.
• The combination of ES and BDNF exerts a synergistic, rather than additive, protective effect.
• Peripheral processes of SGNs play a critical role in auditory sensitivity, potentially more so than SGN bodies.