Neurotrophins differentially stimulate the growth of cochlear neurites on collagen surfaces and in gels  

作　　者：Joanna Xie Kwang Pak Amaretta Evans Andy Kamgar-Parsi Stephen Fausti Lina Mullen Allen Frederic Ryan 

机构地区：[1]Department of Surgery/Otolaryngology, School of Medicine and Veterans Administration Medical Center, University of California [2]National Center for Research on Auditory Rehabilitation, Portland VA Medical Center [3]Department of Neurosciences, School of Medicine and Veterans Administration Medical Center, University of California

出　　处：《Neural Regeneration Research》2013年第17期1541-1550,共10页中国神经再生研究（英文版）

基　　金：supported by grants from the Research Service of the United States Veterans Administration (to Allen Frederic Ryan and Stephen Fausti);the National Institute of Health/National Institute on Deafness and Other Communication Disorders (to Allen Frederic Ryan);the National Institute of Health Summer Research Program (to Joanna Xie);the Deafness Research Foundation (to Lina Mullen);the National Organization for Hearing Research (to Lina Mullen)

摘　　要：The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.The electrodes of a cochlear implant are located far from the surviving neurons of the spiral ganglion, which results in decreased precision of neural activation compared to the normal ear. If the neurons could be induced to extend neurites toward the implant, it might be possible to stimulate more discrete subpopulations of neurons, and to increase the resolution of the device. However, a major barrier to neurite growth toward a cochlear implant is the fluid filling the scala tympani, which separates the neurons from the electrodes. The goal of this study was to evaluate the growth of cochlear neurites in three-dimensional extracellular matrix molecule gels, and to increase biocompatibility by using fibroblasts stably transfected to produce neurotrophin-3 and brain-derived neurotrophic factor. Spiral ganglion explants from neonatal rats were evaluated in cultures. They were exposed to soluble neurotrophins, cells transfected to secrete neurotrophins, and/or collagen gels. We found that cochlear neurites grew readily on collagen surfaces and in three-dimensional collagen gels. Co-culture with cells producing neurotrophin-3 resulted in increased numbers of neurites, and neurites that were longer than when explants were cultured with control fibroblasts stably transfected with green fluorescent protein. Brain-derived neurotrophic factor-producing cells resulted in a more dramatic increase in the number of neurites, but there was no significant effect on neurite length. It is suggested that extracellular matrix molecule gels and cells transfected to produce neurotrophins offer an opportunity to attract spiral ganglion neurites toward a cochlear implant.

关 键 词：neural regeneration peripheral nerve injury cochlear implant inner ear neuron neurite guidance NEUROTROPHIN extracellular matrix collagen gel grants-supported paper NEUROREGENERATION 

分 类 号：R764[医药卫生—耳鼻咽喉科]