中国神经再生研究(英文版)

中国神经再生研究(英文版) ›› 2013, Vol. 8 ›› Issue (17): 1541-1550.doi: 10.3969/j.issn.1673-5374.2013.17.001

• 原著:周围神经损伤修复保护与再生 •    下一篇

胶原凝胶中神经营养因子可刺激耳蜗神经突起的生长

  

  • 收稿日期:2012-12-21 修回日期:2013-02-07 出版日期:2013-06-15 发布日期:2013-06-15

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

Joanna Xie1, Kwang Pak1, Amaretta Evans1, Andy Kamgar-Parsi1, Stephen Fausti2, Lina Mullen1, Allen Frederic Ryan1, 3   

  1. 1 Department of Surgery/Otolaryngology, School of Medicine and Veterans Administration Medical Center, University of California, San Diego, CA 92093-0666, USA
    2 National Center for Research on Auditory Rehabilitation, Portland VA Medical Center, Portland, OR, USA
    3 Department of Neurosciences, School of Medicine and Veterans Administration Medical Center, University of California, San Diego, CA 92093-0666, USA
  • Received:2012-12-21 Revised:2013-02-07 Online:2013-06-15 Published:2013-06-15
  • Contact: Allen Frederic Ryan, Ph.D., Professor, Division of Otolaryngology, School of Medicine, 0666 University of California, San Diego, 9500 Gilman Drive, La Jolla, CA 92093-0666, USA, afryan@ucsd.edu.
  • About author:Joanna Xie☆, Studying for doctorate.

PDF

946

摘要：

耳蜗植入物电极的位置离螺旋神经节存活神经元较远，导致其对神经激活准确性下降。如果神经元能够向植入物发出突起，将使更多散在的神经元被激活，从而提高耳蜗植入物的分辨率。神经突起向耳蜗植入物伸展最大的障碍是鼓阶液，其使神经元与电极相分离。为评估耳蜗神经突起在3D细胞外基质分子凝胶中的生长情况，试图通过应用转染神经营养因子3和脑源性神经营养因子的成纤维细胞，以提高耳蜗神经突起生长效率。将来源于新生大鼠耳蜗螺旋神经节组织块暴露于可溶性神经营养因子及基因转染后可分泌神经营养因子的细胞和/或2-D胶原和3-D凝胶底物中。发现螺旋神经节突起稳定地在2-D胶原、3-D凝胶底物中生长，与分泌神经营养因子3的细胞共培养提高了螺旋神经节突起数量和长度。由此，我们认为细胞外基质分子凝胶和可分泌神经营养因子的细胞为吸引螺旋神经节突起向耳蜗植入物方向生长提供了机会。

关键词: 神经再生, 周围神经损伤, 耳蜗植入物, 内耳, 神经元, 神经突起导向, 神经营养因子, 细胞外基质, 胶原凝胶, 基金资助文章

Abstract:

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.

Key words: neural regeneration, peripheral nerve injury, cochlear implant, inner ear, neuron, neurite guidance, neurotrophin, extracellular matrix, collagen gel, grants-supported paper, neuroregeneration