Gregory R. Bock

Strial dysfunction in mice with cochleo-saccular abnormalities ☆

Most viable dominant spotting (Wv/Wv) mutant mice, which show cochleo-saccular degeneration, were found to have an endocochlear potential (EP) around zero together with a structurally abnormal stria vascularis. Inner hair cells were well preserved, but outer hair cells in the basal half of the cochlea were degenerating, possibly as a result of primary strial dysfunction. Thresholds for the detection of a compound action potential were raised to around 100 dB SPL in the mutants with no EP, and there was little if any cochlear microphonic at the round window. Of the 20 Wv/Wv mice studied, five partially escaped the effects of the mutation and had measurable positive potentials (15-86 mV) in scala media in the basal turn; responses in these animals were intermediate between control responses and those of mutants with no EP. These findings confirm that the pathological processes in this mutant, with cochleo-saccular abnormalities, are fundamentally different from the pathological processes in animals with neuroepithelial abnormalities reported previously [see Steel and Bock (1983) Arch. Otolaryngol. 109, 22-29, for references].

Inner ear pathology in the deafness mutant mouse.

A distinctive cochlear pathology was found in deafness mutant mice. There was a delay in the formation of the fluid-filled Nuel and tunnel spaces in the organ of Corti, the hair cells were distorted and degenerate, and there was poor maintenance of synapses. No hair cells appeared normal by TEM, but SEM revealed some areas where stereocilia appeared relatively normal, suggesting that SEM of the surface of the organ of Corti is not necessarily a good indicator of hair cell pathology in hereditary hearing impairment. Mutant mice show normal development of endocochlear potential, but have no measurable cochlear microphonics or compound action potential. The data suggest that the deafness gene affects the organ of Corti and that cochlear hair cells in deafness mice are never functional.

Cochlear dysfunction in the jerker mouse.

Surface preparations show that the jerker (je/je) mutant mouse has a normal total number of cochlear hair cells when young but that these progressively degenerate with increasing age. However, no gross 8th nerve action potentials or cochlear microphonics could be detected at the round window in 12-20-day-old mutants, although many hair cells still appear to be intact at these ages. Light microscopy of surface preparations is apparently a poor indicator of the functional state of hair cells, at least in genetically determined inner ear defects. The endocochlear potential (EP) was significantly higher in the mutants than in controls during the maturation of the cochlea. During anoxia induced in adults, EP fell to a significantly less negative value in mutants than in control mice. This abnormality in the anoxia potential probably reflects an organ of Corti abnormality.

Effects of N-acetylcysteine on kanamycin ototoxicity in the guinea pig.

It has been suggested that aminoglycoside antibiotics are ototoxic because they create free radicals (reactive oxygen species), which in turn attack membranes. If this hypothesis were correct, then it would be expected that any agent which protects against oxygen-linked toxic effects would ameliorate the ototoxic effects of aminoglycosides. N-Acetylcysteine, a drug in common clinical use, was used to examine this possibility. Three groups of guinea pigs received daily injections for 21 days. One group received 200 mg/kg kanamycin subcutaneously, one group received N-acetylcysteine, while animals in the third group received N-acetylcysteine followed one hour later by kanamycin. After 7 days recovery, all animals, together with a group of control animals receiving no injections, were anaesthetised (neuroleptanalgesia) and thresholds for detection of the compound action potential were measured at the round window. N-Acetylcysteine alone had no detectable effect on thresholds. Kanamycin alone produced a moderate (10–20 dB) hearing loss below 10 kHz and a more severe loss above 10 kHz. Animals receiving both N-acetylcysteine and kanamycin had severe hearing losses (40–60 dB) at all frequencies between 3 and 30 kHz. N-Acetylcysteine had no acute effect on thresholds. The results fail to support the prediction that free radical scavenging protects against kanamycin ototoxicity. On the contrary, N-acetylcysteine exerts a strong synergistic effect on kanamycin, so producing a more severe hearing loss and more severe cochlear damage. The physiological and biochemical bases of this synergy remain to be determined.

Preservation of central auditory function in thedeafness mouse

Deafness mice are profoundly deaf from birth as a result of genetically determined cochlear dysfunction. Evoked potentials in response to direct electrical stimulation of the cochlear nerve can readily be recorded in the inferior colliculus of deafness mice, and such responses are larger in amplitude than those in control mice. These observations indicate that at least some central connections become functional in the deafness central auditory pathway in the absence of peripheral stimulation, and are relevant to the general problem of restoring function by direct nerve stimulation in the profoundly deaf.

Electrically-evoked responses in animals with progressive spiral ganglion degeneration

The deafness (dn/dn) mouse has an hereditary cochlear dysfunction throughout its development, and spiral ganglion cell density decreases progressively over the three age groups we examined. We have used this mutant to examine inferior colliculus evoked responses to modiolar electrical stimulation as a function of spiral ganglion degeneration. No differences were found between mutants and control mice or between ages in either threshold for detection of the response or latency of the response. However, peak-to-peak amplitudes of the response were larger in the mutants than in the controls in the young and intermediate age groups. There was a poor correlation between spiral ganglion degeneration and size of the evoked response: for example, mutants in the old age group had similar amplitudes of response as controls while spiral ganglion cell density was reduced to 21% of the value in young mice, and mutants in the intermediate age group with 50% spiral ganglion degeneration showed response amplitudes more than double that in controls. These data may be relevant to the significant numbers of people with hereditary deafness among the hearing-impaired human population.

Use of albino animals for auditory research

Since Hearing Research commenced publication, 51% of reports involving the use of guinea pigs provide no information on whether the animals used were albino or pigmented. Recent evidence creates a strong suspicion that the albino mutation can influence both peripheral and central auditory function. It is concluded that information on pigmentation should always be provided in reports of auditory experiments on guinea pigs, and that the only justification for using albino animals in auditory research is to study effects of the albino mutation on hearing.

Cochlear potentials in the Bronx waltzer mutant mouse.

The Bronx waltzer mutant mouse has a unique cochlear abnormality in which the outer hair cells appear normal but the inner hair cells are absent. Potentials recorded from the round window indicate that the gross cochlear nerve action potential is very small or absent and cochlear microphonics are present but of small amplitude. Positive and negative summating potentials can both be recorded, indicating that mammalian outer hair cells are capable of producing both positive and negative DC potentials.

Mixed conductive and sensorineural hearing loss in LP/J mice☆

Air and bone conduction thresholds for the detection of a compound action potential response were measured in mice of the LP/J inbred strain, which has been proposed as a possible model for human otosclerosis. Thresholds were compared with control data from CBA/Ca mice. Evidence of a mixed sensorineural and conductive hearing loss was obtained in LP/J mice. Few signs of hair cell degeneration or middle-ear bony lesions were found in 20-day old mice, although they generally showed raised thresholds to both air and bone conducted stimuli. The reason for the observed sensorineural component of the hearing loss at this age is not clear, since endocochlear potentials were normal in mice of this strain. By 225 days of age, hair cell loss was extensive and there was clearly excess bone growth in all middle-ear specimens studied, particularly on the incus and the cochlear wall facing the middle ear. Microbiological analysis of LP/J specimens revealed no evidence of a middle-ear infection specific to these mice which might explain the pathology.

Functional histopathology of the human audio-vestibular organ. Euro-Data-Hearing.

The present paper describes the setting-up of a new project, sponsored by the Commission of the European Communities, to promote the study of functional histopathology of the human audio-vestibular organ. The project has the purpose of co-ordinating in Europe morphological research on the hearing and equilibrium organ and promoting the comparison of data from clinical, physiological and morphological studies in the field of hearing and equilibrium impairment. A manual (Iurato et al., 1982) has been prepared with the objectives of (1) stimulating clinicians to participate in the project, (2) encouraging the collection of audiological data for comparison with pathology, and (3) supplying clinicians with the necessary information about the technique of fixation and preparation of the specimens. The fixation procedures for the two major techniques of studying ear pathology: (1) microdissection and electron microscopy, and (2) embedding of the whole block for serial sectioning and light microscopy, are described in detail. Special paragraphs deal with the technique of fixation of the brain and with the technique of removal of the temporal bones and brain at autopsy. The instructions for delivery of the specimens and the publication rules are enclosed in the main body of the manual. Appendix 1 contains a list of the participating laboratories. Appendix 2 deals with autopsy legislation in the different European countries. Appendix 3 contains the senders data sheet which supplies the instructions for collecting the clinical history of the patient and the audiological and vestibular data.