The use of Neurotrophin Therapy in the Inner Ear to Augment Cochlear Implantation Outcomes

Abstract

This review will cover the roles of neurotrophins in inner ear development, neuronal maintenance, neuronal process regeneration, and clinical applications including possible augmentation of cochlear implant function. Severe to profound deafness is most often secondary to a loss of or injury to cochlear mechanosensory cells, and there is often an associated loss of the peripheral auditory neural structures, specifically the spiral ganglion neurons and peripheral auditory fibers. Cochlear implantation is currently our best hearing rehabilitation strategy for severe to profound deafness. These implants work by directly electrically stimulating the remnant auditory neural structures within the deafened cochlea. When administered to the deafened cochlea in animal models, neurotrophins, specifically BDNF and NT3, have been shown to dramatically improve spiral ganglion neuron survival and stimulate peripheral auditory fiber regrowth. In animal models, neurotrophins administered in combination with cochlear implantation has resulted in significant improvements in the electrophysiological and psychophysical measures of outcome. While further research must be done before these therapies can be applied clinically, neurotrophin therapies for the inner ear show great promise in enhancing cochlear implant outcomes and the treatment of hearing loss.

CaBP1 regulates Cav1 L-type Ca2+ channels and their coupling to neurite growth and gene transcription in mouse spiral ganglion neurons

“…The electrical stimulation provided by cochlear implants is expected to support the survival of SGNs (Hegarty et al, 1997; Miller et al, 2003), but also limit SGN neurite growth (Roehm et al, 2008). In addition to neurotrophin therapy (Budenz et al, 2012), antagonizing CaBP1 signaling could offer a promising approach to overcoming current obstacles in cochlear implant therapies.…”

Targeted delivery of brain-derived neurotrophic factor for the treatment of blindness and deafness

“…145 Beside this, there are two advantages of such anatomical structures: first, the peri-and endolymphatic fluids provide a means for the distribution of BDNF throughout the whole cochlea and, second, BDNF delivered to the inner ear will not reach the systemic circulation, therefore, reducing adverse reactions to the organism. 146 Many experimental models have been presented to cause hearing loss. Traditionally, the combination of aminoglycosides and diuretics is considered to be a classical one.…”

Morphometrical Analysis of Developing Cochlear Ganglion Neurons: A Light Microscopic Fetal Study

“…Recent treatment strategies of bionic cochlear implant use these growth factors to aid survival of cochlear ganglion neurons in deafened ear and enhancing therapeutic outcomes [10]. Many experimental studies have shown that whenever there is loss of neurotrophic support from these factors, the ganglion neurons appear unhealthy with smaller soma [19] and pyknotic, misshapen nuclei [23][24][25].…”

“…Till now various studies have been conducted on developing animals to understand morphometrical maturation of cochlear ganglion with detailed study on experimentally deafened animals to provide an insight for cochlear implant studies [7][8][9][10].…”