Combined BDNF and NT-3 Growth Factor Cocktail Enhanced Neurite Outgrowth in a mouse in vitro and a guinea pig in vivo model

Cochlea implants (CI) are the method of choice for patients suffering from sensorineural hearing loss. A major problem is the spatial gap between the electrode array of the CI and the stimulated region of the auditory nerve. This anatomical gap restricts the number of information channels provided by the implant and leads to high stimulation thresholds and energy consumption. To improve CI performance by bridging this gap, the outgrowth of nerve fibers towards the CI electrode array were stimulated with the growth factors BDNF (brain-derived neurotrophic factor) and NT-3 (neurotrophin 3).

To probe candidate combinations, a mouse organotypic in vitro spiral ganglion explant model at postnatal day 7 was established. The winning combination was evaluated in an in vivo guinea pig model. CI performance was assessed 6 weeks after treatment by electrically evoked compound action potentials (eCAP) recorded from deafened animals.

Under in vitro conditions, the application of BDNF and NT-3 in a ratio of 1:2 showed the best outgrowth performance. The use of BDNF, NT-3 or both in combination resulted in improved CI performance over untreated controls. Overall, the treatments resulted in higher eCAP amplitudes, increased dynamic ranges and reduced stimulation thresholds compared to untreated controls, with a significantly reduced stimulation threshold for the combined BDNF and NT-3 cocktail.

The presented approaches demonstrated to be successful in enhancing neurite outgrowth in vitro and in vivo. Moreover, the in vitro identified neurotrophin cocktail proofed to be superior in improving the CI performance over the level of BDNF and NT-3 applied individually in vivo. Overall, bridging the anatomical gap has the potential to improve CI performance in man in the near future

Poster-PDF A-1878.PDF

Publication History

Article published online:
10 June 2020