Geissler Christin, Blumenstock Miriam, Gabrielpillai Jennis, Guchlerner Leon, Stöver Timo, Diensthuber Marc
Department of Otorhinolaryngology, Head and Neck Surgery, University Hospital Frankfurt, Goethe University, Frankfurt, Germany.
Neuroreport. 2021 Sep 8;32(13):1134-1139. doi: 10.1097/WNR.0000000000001701.
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.
血液流变学药物己酮可可碱被用于治疗突发性感音神经性听力损失和耳鸣，以改善耳蜗微循环。最近的研究还表明其对神经元细胞具有保护和营养作用。由于内耳感觉神经结构的保存对于正常听力以及使用听觉假体恢复听力至关重要，己酮可可碱和神经营养因子，如脑源性神经营养因子（BDNF），是治疗内耳退行性疾病的有前景的候选药物。我们使用体外模型来确定这些因子对新生大鼠螺旋神经节细胞的营养作用。将不同浓度的己酮可可碱单独或与BDNF联合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，己酮可可碱并未显著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，在己酮可可碱存在的情况下会形成多种神经元亚型。我们的数据显示，当同时用己酮可可碱和BDNF处理培养细胞时，己酮可可碱不会干扰BDNF对螺旋神经节神经元的强大营养作用。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，也不会降低BDNF的作用，只要未来的体内实验和临床研究支持这些发现，这两种药物可以联合用于治疗内耳疾病。
