Simultaneous treatment with pentoxifylline does not adversely affect the neurotrophic effects of brain-derived neurotrophic factor on spiral ganglion neurons

Abstract

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.

Molecular and Functional Characterization of BDNF-Overexpressing Human Retinal Pigment Epithelial Cells Established by Sleeping Beauty Transposon-Mediated Gene Transfer

“…BDNF used in this study supports neuronal cell differentiation and maturation and promotes neuronal survival and growth [ 63 , 64 ], possibly through interaction with the Wnt/β-catenin signaling pathway mediated by glycogen synthase kinase-3 beta (GSK-3β) [ 65 ]. Furthermore, the neuroprotective effect of BDNF was also demonstrated in vivo in hypoxic ischemic brain injury [ 66 , 67 ].…”