National Institute of Health
Contract HHS-N-263-2007-00053-C
The Effects of Intracochlear Electrical Stimulation on Neural Survival and Connectivity

We are exploring a new method of delivering neurotrophic factors to the cochlea in combination with electrical stimulation (ES) via a cochlear implant. We believe that this research project constitutes a major step towards the implementation of new techniques to restore hearing to deaf people. The specific aims of this project are to: i) Determine whether neurotrophins will promote auditory neuron survival in a long-term chronically implanted deafened model. ii) Determine whether neurotrophin treatment in combination with a clinical implant, is effective in promoting auditory neuron survival in a long-term deafened model. iii) To examine the electrophysiological function of auditory neurons treated with neurotrophins and cochlear implants.

The team includes Dr Andrew Wise, Ms Jacqueline Andrew, Dr James Fallon, Ms Alison Evans, Ms Meera Ulaganathan, Mr Tom Landry Dr Jin Xu, Ms Helen Feng, and Prof. Rob Shepherd.

The project is also supported by a project grant from The Garnett Passe and Rodney Williams Memorial Foundation.

Electrically evoked response area recorded to identify the best stimulating electrode and the extent of AN activation spread across the stimulating array.

The pro-survival effects of neurotrophin delivery (with or without ICES) following aminoglycoside-induced deafening are well established. What are less clear are the effects of neurotrophin delivery with different deafness pathologies and the effects of neurotrophin delivery and ICES on the spatial and temporal processing ability of the central auditory system. It has been shown that there is profuse dendritic resprouting following aminoglycoside-induced deafening and neurotrophin delivery; however the consequences of this resprouting on the functional cochleotopic organization of the central auditory system are unclear. We are using a combination of single SGN peripheral fibre tracing techniques (to determine the extent of aberrant peripheral fibre regrowth following neurotrophin and / or ICES treatment) and high-resolution spatial response intensity images from multi-channel multi-unit data recorded across the central nucleus of the inferior colliculus (ICC) in response to acute intracochlear electrical stimulation. These experiments will allow us to study the effects of the resprouting from both anatomical and functional perspectives and are vital experiments to be performed before neurotrophins are considered for any clinical application.

The team includes Mr Tom Landry, Dr Andrew Wise, Dr James Fallon, Dr Jin Xu, Ms Helen Feng, and Prof. Rob Shepherd.

Tom Landry is supported by a by The Bartholomew Reardon PhD Scholarship.

Spatial response intensity images from a 6 week deafened Guinea Pig.

While exogenous NT delivery has been shown to promote SGN survival in the deafened cochlea, the clinical application of NTs awaits an acceptable delivery system. The development of a layered nanofilm, sequestering the desired NT, physically designed for implantation in to the cochlea, and engineered for optimal NT release kinetics would offer a potentially elegant solution. We have developmented a bio-compatible bio-degradable nanoparticles containing BDNF which is capable of delivering a sustained slow release of neurotrophin to the cochlea.

The team includes Dr F. Glynn, Dr Justin Tan Prof. Frank Caruso Dr Y. Wang and Prof. Rob Shepherd.

BDNF release was measured by repeated sampling of the supernatant of a solution of nanoparticles followed by an ELISA assay.