title: A model for auditory brain stem implants: bilateral surgical deafferentation of the cochlear nuclei in the macaque monkey.
abstract: BACKGROUND
  Patients with extensive bilateral lesions of the auditory nerve have a profound and irreversible sensorineural hearing loss (SNHL), which can only be overcome with individually-fitted auditory brain stem implants that directly stimulate the cochlear nuclei. Despite the enormous potential of this increasingly applied treatment, the auditory performance of many implanted patients is limited, and the variability between cases hinders a complete understanding of the role played by the multiple parameters related to the efficacy of the implant.
  
  
  OBJECTIVE
  To mimic the condition of patients who have bilateral lesions of the auditory nerve, we developed an experimental model of bilateral deafferentation of the cochlear nuclei by surgical transection of the cochlear nerves of adult primates.
  
  
  METHODS
  We performed bilateral transection of the cochlear nerves of six adult, healthy, male captive-bred macaques (Macaca fascicularis). Before surgery, brain stem auditory evoked potentials were recorded. The histological material obtained from these animals was compared with similarly processed sections from seven macaques with intact cochlear nerves. The surgical technique, similar to that used in human neuro-otology, combined a labyrinthectomy and a neurectomy of the cochlear nerves, and caused deafness. We analyzed immunocytochemically the expression in cochlear nerve fibers of neurofilaments (SMI-32), and cytosolic calcium binding proteins calretinin, parvalbumin and calbindin, and also applied a histochemical reaction for acetylcholinesterase.
  
  
  RESULTS
  None of the primates had any major complications due to the surgical procedure. The lesions produced massive anterograde degeneration of the cochlear nerves, evidenced by marked gliosis and by loss of both type I fibers (which in this species are immunoreactive for calretinin, parvalbumin and neurofilaments) and type II fibers (which are acetylcholinesterase positive). The model of surgical transection described herein causes extensive damage to the cochlear nerves while leaving the cochlea intact, thus mimicking the condition of patients with profound SNHL due to bilateral cochlear nerve degeneration.
  
  
  CONCLUSIONS
  The phylogenetic proximity of primates to humans, and the paramount advantage of close anatomical and physiological similarities, allowed us to use the same surgical technique applied to human patients, and to perform a thorough evaluation of the consequences of neurectomy. Thus, bilateral surgical deafferentation of the macaque cochlear nuclei may constitute an advantageous model for study of auditory brain stem implants.
authors.affiliation: Departamento de Otorrinolaringología, University of Navarra, Clínica Universitaria, Pamplona, Spain. jcervera@unav.es
authors.forename: Francisco Javier
authors.initials: FJ
authors.lastname: Cervera-Paz
authors.forename: Enrique
authors.initials: E
authors.lastname: Saldaña
authors.forename: Manuel
authors.initials: M
authors.lastname: Manrique
mesh_terms: D000818:Animals; D038262:Auditory Brain Stem Implants; D001306:Auditory Pathways / Q000473:pathology / Q000601:surgery*; D001933:Brain Stem / Q000601:surgery*; D017626:Cochlear Nucleus / Q000473:pathology / Q000601:surgery*; D007839:Functional Laterality / Q000502:physiology*; D008252:Macaca fascicularis; D008297:Male; D023421:Models, Animal