BDNF limits cisplatin-induced toxicity to auditory neurons

Introduction:

Cisplatin is an established cytostatic agent in the treatment of head and neck cancer. It exerts its effects by inhibiting DNA replication and induction of apoptosis. An undesirable side effect of cisplatin is ototoxicity, which primarily appears as hair cell damage with hearing loss in the higher frequencies. The study investigated the toxicity pattern of cisplatin on spiral ganglion neurons (SGN) and potential protective effects of brain-derived neurotrophic factor (BDNF) during cell damage.

Material and Methods:

In order to verify the toxicity and protection potential of the two substances, spiral ganglia were dissected from the inner ear of postnatal rats. The cells were cultured with cisplatin (0.1 – 4 µg/ml) and BDNF for 48h and subsequently immunocytochemically detected. The cell cultures were analyzed and the neuronal survival, neurite length, number of branches and morphology were evaluated.

Results:

Addition of cisplatin showed a dose-dependent decrease in survival, neurite length and number of branches of SGN. The maximum toxic effect was detectable at 4 µg/ml cisplatin. When assessing the morphology, addition of cisplatin significantly increased the fraction of monopolar SGNs. Simultaneous application of BDNF reduced cisplatin-induced toxicity on SGNs.

Conclusion:

The data demonstrate the toxicity pattern of cisplatin on SGNs of the inner ear. These toxic effects were successfully limited by BDNF. Thus, the application of BDNF to reduce cisplatin-induced neurotoxicity represents a potential clinical application of the factor in the inner ear.

Publication History

Publication Date:
23 April 2019 (online)