Prevention - and intervention therapies in auditory trauma

Sammanfattning: 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.