NT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells

Staecker, Hinrich; Kopke, Richard D.; Malgrange, Brigitte; Lefèbvre, Philippe; Water, Thomas R. Van De

doi:10.1097/00001756-199603220-00011

Cited by 250 publications

(241 citation statements)

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“…8). Sprouting has been reported previously after infusion of BNDF and NT-3 in deafened guinea pigs (Miller et al, 2007;Staecker et al, 1996;Wise et al, 2005), although in the Wise et al study (with no ICES) the sprouted fibers grew upward into the spiral limbus of the degenerated organ of Corti. Thus, the applied electrical stimulation in our study may have guided or attracted fibers to grow into the region above the electrode within the scala tympani.…”

Section: Intracochlear Infusion Of Neurotrophinsmentioning

confidence: 53%

“…As mentioned previously, several recent in vivo studies have reported that direct cochlear infusion of neurotrophins (NTs), particularly BDNF, can promote improved SG survival following deafness (Gillespie et al, 2003;Miller et al, 1997;Miller et al, 2007;Shinohara et al, 2002;Staecker et al, 1996). Further, ICES has been reported to be additive to the effects of NTs (Kanzaki et al, 2002;Shepherd et al,2005;Pettingill et al, 2007) in reducing SG degeneration.…”

Section: Intracochlear Infusion Of Neurotrophinsmentioning

confidence: 91%

“…Within the developing cochlea, neurotrophins are differentially distributed, with NT-3 expressed predominantly in the supporting cells of the organ of Corti, and BDNF expressed only in hair cells (Farinas, et al, 2001). Further, many in vivo studies have reported that exogenous administration of neurotrophins (Ernfors et al, 1996;Kanzake et al, 2002;McGuinnes and Shepherd, 2005;Miller et al, 1997;Schindler et al 1995;Shepherd et al, 2005;Staecker et al, 1996Staecker et al, , 1998Zheng et al, 1995;Zheng and Gao, 1996) and other neurotrophic factors such as glial cell line-derived neurotrophic factor (GDNF) (Ylikoski et al, 1998;Yagi et al, 2000) can protect SG neurons in adult animals from injury and promote improved survival after various insults, including ototoxic drugs.…”

Section: The Role Of Neurotrophins In Survival Of Sg Neurons After Nementioning

confidence: 99%

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Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

et al. 2008

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Research in animal models has demonstrated that electrical stimulation from a cochlear implant (CI) may help prevent degeneration of the cochlear spiral ganglion (SG) neurons after deafness. In cats deafened early in life, effective stimulation of the auditory nerve with complex signals for several months preserved a greater density of SG neurons in the stimulated cochleae as compared to the contralateral deafened ear. However, SG survival was still far from normal even with early intervention with an implant. Thus, pharmacologic agents and neurotrophic factors that might be used in combination with an implant are of great interest. Exogenous administration of GM1 ganglioside significantly reduces SG degeneration in deafened animals studied at 7-8 weeks of age, but after several months of stimulation, GM1-treated animals show only modestly better preservation of SG density compared to age-matched non-treated animals. A significant factor influencing neurotrophic effects in animal models is insertion trauma, which results in significant regional SG degeneration. Thus, an important goal is to further improve human CI electrode designs and insertion techniques to minimize trauma.Another important issue for studies of neurotrophic effects in the developing auditory system is the potential role of critical periods. Studies examining animals deafened at 30 days of age (rather than at birth) have explored whether a brief initial period of normal auditory experience affects the vulnerability of the SG or cochlear nucleus (CN) to auditory deprivation. Interestingly, SG survival in animals deafened at 30-days was not significantly different from age-matched neonatally deafened animals, but significant differences were observed in the central auditory system. CN volume was significantly closer to normal in the animals deafened at 30 days as compared to neonatally deafened animals. However, no difference was observed between the stimulated and contralateral CN volumes in either deafened group. Measurements of AVCN spherical cell somata showed that after later onset of deafness in the 30-day deafened group, mean cell size was significantly closer to normal than in the neonatally deafened group. Further, electrical stimulation elicited a significant increase in spherical cell size in the CN ipsilateral to the implant as compared to the contralateral CN in both deafened groups.Neuronal tracer studies have examined the primary afferent projections from the SG to the CN in neonatally deafened cats. CN projections exhibit a clear cochleotopic organization despite severe auditory deprivation from birth. However, when normalized for the smaller CN size after deafness, projections were 30-50% broader than normal. After unilateral electrical stimulation there was no difference between projections from the stimulated and non-stimulated ears. These findings suggest that early normal auditory experience may be essential for the normal development (or subsequent Publisher's Disclaimer: This is a PDF file of an unedited manuscript...

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Section: Intracochlear Infusion Of Neurotrophinsmentioning

confidence: 53%

Section: Intracochlear Infusion Of Neurotrophinsmentioning

confidence: 91%

Section: The Role Of Neurotrophins In Survival Of Sg Neurons After Nementioning

confidence: 99%

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Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

et al. 2008

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“…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]. Other experimental studies on deafened animals have shown that on treatment with exogenous neurotrohic factors, the surviving spiral ganglion neurons appeared larger, and healthier with well defined nucleus, nucleolus and abundant Nissl substance [19,26].…”

Section: Resultsmentioning

confidence: 99%

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

Sethi¹

2015

JCDR

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“…Previous studies have shown that chronic delivery of neurotrophic factors such as brain derived neurotrophic factor (BDNF), neurotrophin-3 or GDNF can prevent the degeneration of spiral ganglion neurons (Staecker et al, 1996;Miller et al, 1997;Shinohara et al, 2002;Gillespie et al, 2003) and that chronic electrical stimulation promotes survival of these cells in the deafened cochlea (Lousteau, 1987;Leake et al, 1991;Leake et al, 1999;Leake and Rebscher, 2004). Furthermore, Shepherd et al (2005) suggested that application of electrical stimulation and neurotrophic factors concurrently may have an additive effect.…”

Section: Integrated Drug Deliverymentioning

confidence: 99%

Design and fabrication of multichannel cochlear implants for animal research

Rebscher

Hetherington

Snyder

et al. 2007

Journal of Neuroscience Methods

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NT-3 and/or BDNF therapy prevents loss of auditory neurons following loss of hair cells

Cited by 250 publications

References 0 publications

Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

Factors influencing neurotrophic effects of electrical stimulation in the deafened developing auditory system

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

Design and fabrication of multichannel cochlear implants for animal research

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