Direct administration of 2-Hydroxypropyl-Beta-Cyclodextrin into guinea pig cochleae: Effects on physiological and histological measurements

Autor: R. K. Duncan, Jeffery T. Lichtenhan, Keiko Hirose, Craig A. Buchman, Alec N. Salt
Jazyk: angličtina
Rok vydání: 2017
Předmět:
Male
Physiology
Sensory Physiology
lcsh:Medicine
Beta-Cyclodextrins
Audiology
01 natural sciences
0302 clinical medicine
Medicine and Health Sciences
lcsh:Science
010301 acoustics
Organ of Corti
Mammals
Multidisciplinary
Chemistry
beta-Cyclodextrins
Animal Models
Salicylates
3. Good health
Cochlea
2-Hydroxypropyl-beta-cyclodextrin
Electrophysiology
medicine.anatomical_structure
Experimental Organism Systems
Toxicity
Physical Sciences
Inner Ear
Vertebrates
Female
medicine.symptom
Anatomy
Salicylic Acid
Research Article
medicine.medical_specialty
Cochlear amplifier
Histology
Hearing loss
Guinea Pigs
Research and Analysis Methods
Rodents
Membrane Potential
03 medical and health sciences
Internal medicine
0103 physical sciences
medicine
otorhinolaryngologic diseases
Animals
lcsh:R
Chemical Compounds
Organisms
Biology and Life Sciences
Excitatory Postsynaptic Potentials
Perilymph
Endocrinology
Ears
Amniotes
Cochlear aqueduct
lcsh:Q
sense organs
Head
Acids
030217 neurology & neurosurgery
Zdroj: PLoS ONE, Vol 12, Iss 4, p e0175236 (2017)
PLoS ONE
ISSN: 1932-6203
Popis: 2-Hydroxypropyl-Beta-Cyclodextrin (HPβCD) can be used to treat Niemann-Pick type C disease, Alzheimer's disease, and atherosclerosis. But, a consequence is that HPβCD can cause hearing loss. HPβCD was recently found to be toxic to outer hair cells (OHCs) in the organ of Corti. Previous studies on the chronic effects of in vivo HPβCD toxicity did not know the intra-cochlear concentration of HPβCD and attributed variable effects on OHCs to indirect drug delivery to the cochlea. We studied the acute effects of known HPβCD concentrations administered directly into intact guinea pig cochleae. Our novel approach injected solutions through pipette sealed into scala tympani in the cochlear apex. Solutions were driven along the length of the cochlear spiral toward the cochlear aqueduct in the base. This method ensured that therapeutic levels were achieved throughout the cochlea, including those regions tuned to mid to low frequencies and code speech vowels and background noise. A wide variety of measurements were made. Results were compared to measurements from ears treated with the HPβCD analog methyl-β-cyclodextrin (MβCD), salicylate that is well known to attenuate the gain of the cochlear amplifier, and injection of artificial perilymph alone (controls). Histological data showed that OHCs appeared normal after treatment with a low dose of HPβCD, and physiological data was consistent with attenuation of cochlear amplifier gain and disruption of non-linearity associated with transferring acoustic sound into neural excitation, an origin of distortion products that are commonly used to objectively assess hearing and hearing loss. A high dose of HPβCD caused sporadic OHC losses and markedly affected all physiologic measurements. MβCD caused virulent destruction of OHCs and physiologic responses. Toxicity of HPβCD to OHC along the cochlear length is variable even when a known intra-cochlear concentration is administered, at least for the duration of our acute studies.
Databáze: OpenAIRE
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