Electrophysiological correlates of progressive sensorineural pathology in carboplatin-treated chinchillas

Brain Res. 2007 Feb 23;1134(1):122-30. doi: 10.1016/j.brainres.2006.11.078. Epub 2007 Jan 2.

Abstract

Carboplatin produces progressive damage to auditory nerve fibers, spiral ganglion neurons (SGNs) and inner hair cells (IHC) in the chinchilla cochlea but leaves outer hair cells intact. Within 1 h after injection, many afferent terminals beneath IHCs and myelin lamellae surrounding SGN processes are vacuolated. One day after injection, approximately half of the nerve fibers are missing. IHCs are intact at 2 days, but 20-30% are missing at 3 days. We studied the electrophysiological correlates of this progressive morphological damage by recording cochlear microphonics (CM), distortion product otoacoustic emissions (DPOAE), summating potentials (SP), compound action potentials (CAP) and midbrain evoked potentials (IC-EVP) before and 1 h, 12 h, 1 days, 3 days, 5 days, 7 days and 14 days after carboplatin injection (75 mg/kg IP) in four chinchillas. CM and DPOAEs tended to be unchanged or enhanced. CAP and SP showed little change until Day 3, when amplitudes were reduced in all animals and CAP thresholds were elevated by 9 dB; amplitudes declined further between Days 3 and 5 but not thereafter. IC-EVP amplitudes decreased on Days 3 or 5 but thresholds were relatively unchanged. All animals showed some recovery of IC-EVP between Days 7 and 14, including one with 70% enhancement on Day 14. The results indicate that threshold and amplitude measures fail to detect peripheral pathology until some relatively high threshold level of damage has been exceeded. This has important implications for monitoring peripheral damage and interpreting electrophysiological test results in animals and humans.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Acoustic Stimulation
  • Action Potentials / drug effects
  • Action Potentials / physiology
  • Animals
  • Antineoplastic Agents / toxicity
  • Auditory Threshold / drug effects
  • Auditory Threshold / physiology
  • Carboplatin / toxicity*
  • Chinchilla
  • Cochlea / drug effects*
  • Cochlea / pathology
  • Cochlea / physiopathology
  • Cochlear Nerve / drug effects*
  • Cochlear Nerve / pathology
  • Cochlear Nerve / physiopathology
  • Disease Progression
  • Evoked Potentials, Auditory, Brain Stem / drug effects
  • Evoked Potentials, Auditory, Brain Stem / physiology
  • Hair Cells, Auditory, Inner / drug effects
  • Hair Cells, Auditory, Inner / pathology
  • Hair Cells, Auditory, Inner / physiopathology
  • Hearing Loss, Sensorineural / chemically induced*
  • Hearing Loss, Sensorineural / pathology
  • Hearing Loss, Sensorineural / physiopathology
  • Neural Conduction / drug effects
  • Neural Conduction / physiology
  • Spiral Ganglion / drug effects
  • Spiral Ganglion / pathology
  • Spiral Ganglion / physiopathology

Substances

  • Antineoplastic Agents
  • Carboplatin