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Simultaneous treatment with pentoxifylline does not adversely affect the neurotrophic effects of brain-derived neurotrophic factor on spiral ganglion neurons.
Neuroreport ( IF 1.7 ) Pub Date : 2021-07-19 , DOI: 10.1097/wnr.0000000000001701
Christin Geissler 1 , Miriam Blumenstock , Jennis Gabrielpillai , Leon Guchlerner , Timo Stöver , Marc Diensthuber
Affiliation  

The hemorheologic drug pentoxifylline is applied for the treatment of sudden sensorineural hearing loss and tinnitus to improve cochlear microcirculation. Recent studies also suggest protective and trophic effects on neuronal cells. Because the preservation of sensorineural structures of the inner ear is fundamental for normal hearing and hearing restoration with auditory prostheses, pentoxifylline and neurotrophic factors such as brain-derived neurotrophic factor (BDNF) are promising candidates to treat degenerative disorders of the inner ear. We used an in-vitro model to determine the neurotrophic effects of these factors on spiral ganglion cells from postnatal rats. Pentoxifylline, alone and in combination with BDNF, was added at various concentrations to the cultured cells. Cells were immunolabeled and analyzed to determine neuronal survival, neurite length, neuronal branching and morphology. Pentoxifylline did not significantly increase or decrease neuronal survival, neurite length and neuronal branching compared to control cultures. Analysis of cellular morphology showed that diverse neuronal subtypes developed in the presence of pentoxifylline. Our data revealed that pentoxifylline did not interfere with the robust neurotrophic effects of BDNF on spiral ganglion neurons when cultured cells were treated with pentoxifylline and BDNF simultaneously. The results of our study do not suggest major neurotrophic effects of pentoxifylline on cultured spiral ganglion neurons. Because pentoxifylline has no detrimental effects on spiral ganglion neurons and does not reduce the effects of BDNF, both agents could be combined to treat diseases of the inner ear provided that future in vivo experiments and clinical studies support these findings.

中文翻译:

同时用己酮可可碱治疗不会对脑源性神经营养因子对螺旋神经节神经元的神经营养作用产生不利影响。

血液流变药物己酮可可碱用于治疗突发感音神经性耳聋和耳鸣,改善耳蜗微循环。最近的研究还表明对神经元细胞有保护和营养作用。由于保留内耳感觉神经结构对于正常听力和听觉假体听力恢复至关重要,因此己酮可可碱和神经营养因子(例如脑源性神经营养因子(BDNF))是治疗内耳退行性疾病的有希望的候选药物。我们使用体外模型来确定这些因子对产后大鼠螺旋神经节细胞的神经营养作用。将己酮可可碱单独或与 BDNF 组合以不同浓度添加到培养的细胞中。对细胞进行免疫标记和分析,以确定神经元存活、神经突长度、神经元分支和形态。与对照培养物相比,己酮可可碱没有显着增加或减少神经元存活、神经突长度和神经元分支。细胞形态分析表明,在己酮可可碱存在下,多种神经元亚型形成。我们的数据显示,当培养的细胞同时用己酮可可碱和 BDNF 处理时,己酮可可碱不会干扰 BDNF 对螺旋神经节神经元的强大神经营养作用。我们的研究结果并未表明己酮可可碱对培养的螺旋神经节神经元有主要的神经营养作用。由于己酮可可碱对螺旋神经节神经元没有有害影响,并且不会降低 BDNF 的影响,因此只要未来的体内实验和临床研究支持这些发现,这两种药物就可以联合治疗内耳疾病。
更新日期:2021-07-22
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