Neurotrophins and their role in the cochlea

Ramekers, Dyan; Versnel, Huib; Grolman, Wilko; Klis, Sjaak F.L.

doi:10.1016/j.heares.2012.03.002

Cited by 95 publications

(83 citation statements)

References 149 publications

(226 reference statements)

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“…However, the same studies show that many other pediatric CI recipients lag far behind in language development. Thus, we suggest that it is critically important to better understand the specific factors and mechanisms underlying SG degeneration following early onset deafness and the role of neurotrophins (for review see Ramekers et al 2012). To our knowledge, our studies are the first to report on the effects of exogenous neurotrophins combined with electrical stimulation in deafened, developing animals.…”

Section: Discussionmentioning

confidence: 99%

“…These methods may provide better alternatives in the future, but they are still under development and concerns about potential side effects and risks have not yet been adequately addressed. For recent reviews see: Ramekers et al (2012) and Shibata et al (2010).…”

Section: Discussionmentioning

confidence: 99%

“…Many previous studies have reported that exogenous NTs delivered directly to the cochlea in adult animals can protect SG neurons and promote their survival after various insults (Ramekers et al 2012). Recent studies have shown highly significant effects of BDNF in promoting SG survival (Agterberg et al 2008;Glueckert et al 2008;Miller et al 2007;Shepherd et al 2008;Wise et al 2005), and trophic effects also have been reported with other neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) (Kanzaki et al 2002;Maruyama et al 2008;Yagi et al 2000;Ylikoski et al 1998) and fibroblast growth factor (FGF) (Glueckert et al 2008).…”

Section: Introductionmentioning

confidence: 99%

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Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

Leake

Stakhovskaya

Hetherington

et al. 2013

JARO

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Both neurotrophic support and neural activity are required for normal postnatal development and survival of cochlear spiral ganglion (SG) neurons. Previous studies in neonatally deafened cats demonstrated that electrical stimulation (ES) from a cochlear implant can promote improved SG survival but does not completely prevent progressive neural degeneration. Neurotrophic agents combined with an implant may further improve neural survival. Short-term studies in rodents have shown that brain-derived neurotrophic factor (BDNF) promotes SG survival after deafness and may be additive to trophic effects of stimulation. Our recent study in neonatally deafened cats provided the first evidence of BDNF neurotrophic effects in the developing auditory system over a prolonged duration Leake et al. (J Comp Neurol 519:1526-1545. Ten weeks of intracochlear BDNF infusion starting at 4 weeks of age elicited significant improvement in SG survival and larger soma size compared to contralateral. In the present study, the same deafening and BDNF infusion procedures were combined with several months of ES from an implant. After combined BDNF + ES, a highly significant increase in SG numerical density (950 % improvement re: contralateral) was observed, which was significantly greater than the neurotrophic effect seen with ES-only over comparable durations. Combined BDNF + ES also resulted in a higher density of myelinated radial nerve fibers within the osseous spiral lamina. However, substantial ectopic and disorganized sprouting of these fibers into the scala tympani also occurred, which may be deleterious to implant function. EABR thresholds improved (re: initial thresholds at time of implantation) on the chronically stimulated channels of the implant. Terminal electrophysiological studies recording in the inferior colliculus (IC) revealed that the basic cochleotopic organization was intact in the midbrain in all studied groups. In deafened controls or after ES-only, lower IC thresholds were correlated with more selective activation widths as expected, but no such correlation was seen after BDNF + ES due to much greater variability in both measures.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

Leake

Stakhovskaya

Hetherington

et al. 2013

JARO

View full text Add to dashboard Cite

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“…This degeneration has been associated with discontinued neurotrophic support from the organ of Corti (Ernfors et al 1995;Fritzsch et al 1999;Zilberstein et al 2012). Administration of exogenous neurotrophic factors has prevented SGC degeneration in multiple animal models of SNHL (for a review, see Ramekers et al 2012); SGCs are larger and more numerous after neurotrophic treatment than in untreated controls (Ernfors et al 1996;Richardson et al 2005;Shepherd et al 2005;Glueckert et al 2008;Agterberg et al 2008Agterberg et al , 2009Leake et al 2011;van Loon et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Auditory-Nerve Responses to Varied Inter-Phase Gap and Phase Duration of the Electric Pulse Stimulus as Predictors for Neuronal Degeneration

Ramekers

Versnel

Strahl

et al. 2014

JARO

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155

268

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After severe hair cell loss, secondary degeneration of spiral ganglion cells (SGCs) is observed-a gradual process that spans years in humans but only takes weeks in guinea pigs. Being the target for cochlear implants (CIs), the physiological state of the SGCs is important for the effectiveness of a CI. For assessment of the nerve's state, focus has generally been on its response threshold. Our goal was to add a more detailed characterization of SGC functionality. To this end, the electrically evoked compound action potential (eCAP) was recorded in normal-hearing guinea pigs and guinea pigs that were deafened 2 or 6 weeks prior to the experiments. We evaluated changes in eCAP characteristics when the phase duration (PD) and inter-phase gap (IPG) of a biphasic current pulse were varied. We correlated the magnitude of these changes to quantified histological measures of neurodegeneration (SGC packing density and SGC size). The maximum eCAP amplitude, derived from the input-output function, decreased after deafening, and increased with both PD and IPG. The eCAP threshold did not change after deafening, and decreased with increasing PD and IPG. The dynamic range was wider for the 6-weeks-deaf animals than for the other two groups. Excitability increased with IPG (steeper slope of the input-output function and lower stimulation level at the half-maximum eCAP amplitude), but to a lesser extent for the deafened animals than for normal-hearing controls. The latency was shorter for the 6-weeks-deaf animals than for the other two groups. For several of these eCAP characteristics, the effect size of IPG correlated well with histological measures of degeneration, whereas effect size of PD did not. These correlations depend on the use of high current levels, which could limit clinical application. Nevertheless, their potential of these correlations towards assessment of the condition of the auditory nerve may be of great benefit to clinical diagnostics and prognosis in cochlear implant recipients.

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“…Previous reports indicated that neurotrophin receptor signalling is important to prevent the degeneration of SGNs. [4][5][6][7] We showed that EA stimulation significantly increased the expression of receptor tyrosine kinases in the SGNs of p75(−/−) mice cochleae (figure 2). However, elucidation of the functional roles of EA stimulation on progressive hearing loss remains a primary goal of future research.…”

mentioning

confidence: 93%

Therapeutic Effect of Electroacupuncture in a P75 Knockout Mouse Model of Progressive Hearing Loss

et al. 2014

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Neurotrophins and their role in the cochlea

Cited by 95 publications

References 149 publications

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

Effects of Brain-Derived Neurotrophic Factor (BDNF) and Electrical Stimulation on Survival and Function of Cochlear Spiral Ganglion Neurons in Deafened, Developing Cats

Auditory-Nerve Responses to Varied Inter-Phase Gap and Phase Duration of the Electric Pulse Stimulus as Predictors for Neuronal Degeneration

Therapeutic Effect of Electroacupuncture in a P75 Knockout Mouse Model of Progressive Hearing Loss

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