Functional regeneration of the axotomized auditory nerve with combined neurotrophic and anti-inhibitory strategies.
Injury to the mammalian auditory nerve is associated with a lack of long-distance elongation and leads to definitive loss of the hearing function. To overcome this central nervous system typical lack of functional regeneration, a combined neurotrophic and antiinhibitory treatment is applied. After complete unilateral sectioning of the auditory nerve in adult rats a combination of the Nogo-A inhibitor IN-1 and the neurotrophic factor NT-3 is administrated intrathecally into the cerebellopontine angle for one week. Functional regeneration is evaluated by measuring auditory brainstem evoked potentials for a follow-up period of up to three months. After treatment, up to forty percent of the animals showed a second vertex-positive wave in the auditory brainstem evoked potentials which occurred between three to four weeks after sectioning and remained stable during the follow-up period. A limited degree of functional regeneration of the axotomized auditory nerve is possible after application of IN-1 and NT-3. For additional improvement of functional results further investigations on combined treatments with scar reducing agents, neurotrophic factors and neuroprotective drugs remain necessary.
Department of Neurosurgery, Eberhard-Karls-University, Tuebingen, Germany.
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Gharabaghi
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Tatagiba
D000818:Animals; D000911:Antibodies, Monoclonal / Q000008:administration & dosage*; D019771:Axotomy; D003056:Cochlear Nerve / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology* / Q000601:surgery; D004338:Drug Combinations; D005072:Evoked Potentials, Auditory / Q000187:drug effects*; D007278:Injections, Spinal; D009185:Myelin Proteins / Q000037:antagonists & inhibitors; D009416:Nerve Regeneration / Q000187:drug effects / Q000502:physiology*; D020933:Neurotrophin 3 / Q000008:administration & dosage*; D000070798:Nogo Proteins; D051381:Rats; D011917:Rats, Inbred Lew; D020127:Recovery of Function / Q000187:drug effects* / Q000502:physiology
D000911:Antibodies, Monoclonal; D004338:Drug Combinations; D009185:Myelin Proteins; D020933:Neurotrophin 3; D000070798:Nogo Proteins; C000603197:Rtn4 protein, rat