Abstract
Hearing impairment is one of the most common health conditions in
developed countries. It is estimated that approximately 70 million people
worldwide are deaf. For patients with a severe to profound hearing loss a
cochlear implant (CI) is the only treatment today.
The function of a CI depends in part of the survival and electrical
responsiveness of the spiral ganglion neurons (SGNs), the target of the
CI. In order to access the electrical responsiveness in animal models,
electrically-evoked auditory brainstem responses (eABRs) were recorded.
The survival of SGN was estimated by calculating the density of the SGN
in Rosenthal´s canal.
Neurotrophic factors due to their neurotrophic support in the cochlea are
important in the development and maintenance of the auditory system.
Therefore we performed two studies with glial cell line-derived
neurotrophic factor (GDNF) treatment, one acute and one with a delayed
onset of GDNF treatment. Normal hearing guinea pigs were deafened
intracochlear (acute) or by transtympanic injection (delayed) with
neomycin. The animals received a CI that consisted of a combined
electrode (for eABR measurement) and cannula (for intracochlear
infusion). Animals were treated in both studies with GDNF for 4 weeks.
The study with delayed onset also received a posttreatment with daily
injections (i.p.) of antioxidants or saline. Control animals were
deafened and received intracochlear infusion of artificial perilymph.
Nucelosides and nucleotides are known to function as neurotransmitters
and neuromodulater and have recently been shown to have a neurotrophic
effect on neurons. Here we tested UTP and uridine in an acute study on
deafened guinea pigs. Electrical responsiveness was recorded by eABR
measurements and the density of the SGN was investigated.
Both studies with GDNF treatment showed a significant difference in eABR
thresholds (p<0.001) and SGN density (p<0.001) compared to the control
groups. Furthermore, UTP and uridine showed similar results even if not
so pronounced.
We concluded that GDNF treatment in deafened animals inhibits the
degeneration of the SGN even 4 weeks after end of treatment. It is
possible that after a critical time following inner ear trauma endogenous
survival factors are activated and able to maintain the surviving SGN
population. Nucleotides and nucleosides are novel drugs in inner ear
treatment and it is possible that drugs acting on purinoreceptors can be
of clinical interest for developing new treatment strategies for the
injured inner ear.
