Inner Ear Therapy for Neural Preservation

Abstract

A gradual loss of auditory neurons often occurs following sensorineural hearing loss. Since the cochlear implant must stimulate the remaining auditory neuron population, it would be beneficial to preserve as many auditory neurons as possible. Neurotrophic factors protect auditory neurons from degradation after sensorineural hearing loss in experimental animals, but have not yet been translated into the clinical setting. Current experimental and clinical techniques for drug delivery to the inner ear are examined in this review, covering the routes for drug delivery to the cochlea and the delivery systems used to introduce them. Duration of treatment, drug diffusion, effectiveness and safety are discussed with references to how they may be translated to the implementation of neurotrophic factor treatment for neural preservation.

Combined application of brain-derived neurotrophic factor and neurotrophin-3 and its impact on spiral ganglion neuron firing properties and hyperpolarization-activated currents

“…As a result the application of these exogenous neurotrophins has become a leading candidate as an adjunct treatment for cochlear implant recipients (as reviewed by O'Leary et al, 2009;Pettingill et al, 2007;Richardson et al, 2006). Yet separately, BDNF and NT3 have each revealed themselves to be potent modulators of neural activity in peripheral and central auditory systems (Adamson et al, 2002a;Jimenez et al, 1997;Youssoufian and Walmsley, 2007;Zhou et al, 2005).…”

Adenosine amine congener mitigates noise-induced cochlear injury

“…These prophylactic medications were applied topically to the round window membrane (RWM) of the cochlea before noise exposure. Even though the RWM is the most surgically accessible route for drug delivery to the inner ear, it is still problematic because the substances placed onto the RWM do not distribute evenly through the cochlea, and it is difficult to use this route of administration for chronic clinical treatments [15].…”

Neurite outgrowth on cultured spiral ganglion neurons induced by erythropoietin

“…Various neurotrophic factors have been identified to induce trophic and regenerative effects on SGN. Among these, brain-derived neurotrophic factor (BDNF), neurotrophin-3 and neurotrophin-4 play a pivotal role in the protection of SGN and enhance the excitability of the nerve fibers after hair cell loss (Gillespie and Shepherd, 2005;Richardson et al, 2006). Erythropoietin (EPO), the principal modulator of erythropoiesis and regulator of erythrocyte progenitors (for review see Brines and Cerami (2005)), is also known as a potent promoter of neuronal survival.…”