title: In vivo infusion of UTP and uridine to the deafened guinea pig inner ear: effects on response thresholds and neural survival.
abstract: Nucleotides and nucleosides are known to function as neurotransmitters and neuromodulators but have recently been shown to have a trophic effect on neurons. It has previously been shown, in an animal model for cochlear implants, that local infusion of neurotrophic factors intervenes with the degenerative processes occurring after deafening and protects the auditory spiral ganglion neurons so that electrical responsiveness is maintained. Here we test the hypothesis that nucleosides and nucleotides have a similar effect on the acutely damaged inner ear. Pigmented guinea pigs received a cochlear implant electrode for measuring electrically evoked auditory brainstem responses and a miniosmotic pump for delivering drugs directly to the cochlea. The animals were deafened by a 48-hr infusion with 10% neomycin, followed by 23 days of treatment with primarily UTP, uridine nucleotides, or as control artificial perilymph. Electrically evoked responses were measured weekly, and at the end of the experiment the cochleae were collected and processed for morphological analysis and spiral ganglion neuron counting. Both UTP- and uridine-treated groups showed significantly better response after 23 days of treatment compared with the control group. The densities of spiral ganglion neuron were significantly higher for both treated groups compared with the control group treated with artificial perilymph. The results demonstrate that UTP and uridine rescue auditory neurons and suggest that drugs acting on purinoceptors could be of clinical importance.
authors.affiliation: Center for Hearing and Communication Research and Department of Clinical Neuroscience, Karolinska Institutet, Stockholm, Sweden.
authors.forename: Anette
authors.initials: A
authors.lastname: Fransson
authors.forename: Leif E
authors.initials: LE
authors.lastname: Järlebark
authors.forename: Mats
authors.initials: M
authors.lastname: Ulfendahl
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001309:Auditory Threshold / Q000187:drug effects; D002452:Cell Count; D002470:Cell Survival / Q000187:drug effects; D003051:Cochlea / Q000187:drug effects* / Q000503:physiopathology; D003638:Deafness / Q000188:drug therapy* / Q000503:physiopathology*; D004558:Electric Stimulation; D004567:Electrodes, Implanted; D016057:Evoked Potentials, Auditory, Brain Stem / Q000187:drug effects; D006168:Guinea Pigs; D009474:Neurons / Q000187:drug effects / Q000502:physiology; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D013136:Spiral Ganglion / Q000187:drug effects / Q000503:physiopathology; D014529:Uridine / Q000627:therapeutic use*; D014544:Uridine Triphosphate / Q000627:therapeutic use*
chemical_list: D018696:Neuroprotective Agents; D014544:Uridine Triphosphate; D014529:Uridine