Schwieger Jana, Warnecke Athanasia, Lenarz Thomas, Esser Karl-Heinz, Scheper Verena
Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Institute of Zoology, University of Veterinary Medicine Hannover, Foundation, Hannover, Germany.
Department of Otolaryngology, Hannover Medical School, Hannover, Germany; Cluster of Excellence Hearing4all, German Research Foundation, Hannover, Germany.
PLoS One. 2015 Aug 11;10(8):e0133680. doi: 10.1371/journal.pone.0133680. eCollection 2015.
The functionality of cochlear implants (CI) depends, among others, on the number and excitability of surviving spiral ganglion neurons (SGN). The spatial separation between the SGN, located in the bony axis of the inner ear, and the CI, which is inserted in the scala tympani, results in suboptimal performance of CI patients and may be decreased by attracting the SGN neurites towards the electrode contacts. Neurotrophic factors (NTFs) can support neuronal survival and neurite outgrowth.
Since brain-derived neurotrophic factor (BDNF) is well known for its neuroprotective effect and ciliary neurotrophic factor (CNTF) increases neurite outgrowth, we evaluated if the combination of BDNF and CNTF leads to an enhanced neuronal survival with extended neurite outgrowth. Both NTFs were added in effective high concentrations (BDNF 50 ng/ml, CNTF 100 ng/ml), alone and in combination, to cultured dissociated SGN of neonatal rats for 48 hours.
The neuronal survival and neurite outgrowth were significantly higher in SGN treated with the combination of the two NTFs compared to treatment with each factor alone. Additionally, with respect to the morphology, the combination of BDNF and CNTF leads to a significantly higher number of bipolar neurons and a decreased number of neurons without neurites in culture.
The combination of BDNF and CNTF shows a great potential to increase the neuronal survival and the number of bipolar neurons in vitro and to regenerate retracted nerve fibers.
人工耳蜗(CI)的功能尤其取决于存活的螺旋神经节神经元(SGN)的数量和兴奋性。位于内耳骨轴内的SGN与植入鼓阶的CI之间存在空间分离,这导致CI患者的性能欠佳,而将SGN神经突吸引至电极触点可能会减少这种情况。神经营养因子(NTF)可支持神经元存活和神经突生长。
由于脑源性神经营养因子(BDNF)以其神经保护作用而闻名,睫状神经营养因子(CNTF)可增加神经突生长,因此我们评估了BDNF和CNTF的组合是否会导致神经元存活增强以及神经突生长延长。将两种NTF均以有效的高浓度(BDNF 50 ng/ml,CNTF 100 ng/ml)单独或联合添加到新生大鼠的培养解离SGN中,作用48小时。
与单独使用每种因子处理相比,用两种NTF联合处理的SGN中神经元存活和神经突生长明显更高。此外,就形态而言,BDNF和CNTF的组合导致培养物中双极神经元数量明显增加,无神经突的神经元数量减少。
BDNF和CNTF的组合在体外增加神经元存活和双极神经元数量以及使回缩的神经纤维再生方面显示出巨大潜力。