Otolaryngology - Theses
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ItemSystemic steroid protects residual hearing in a guinea pig model of cochlear implantation( 2011)Background: The protection of residual hearing is an important goal of cochlear implant surgery. Local application of steroids to the round window membrane (RWM) of the guinea pig prior to cochleostomy has been shown to protect hearing, but requires a period of pre-treatment for at least one hour. To determine whether this waiting period can be avoided, the efficacy of administering systemic steroids prior to cochlear implantation is investigated. Methods: Seventeen normal hearing guinea pigs were randomly assigned to receive a single preoperative intravenous injection of: 1) normal saline, 2) dexamethasone 0.2 mg/kg or 3) dexamethasone 2 mg/kg, 60 minutes before cochlear implantation. Implantation was completed with a silastic/platinum dummy electrode. Prior to surgery pure tone auditory brainstem response (ABR) thresholds were estimated from both ears separately in response to tone-pips from 2-32 kHz. This was again completed at 1 and 4 weeks postoperatively. The primary outcome measure was threshold shift at 1 and 4 weeks. Histology was examined for evidence of insertion trauma and foreign body reaction. Results: Preoperative injection of 2 mg/kg dexamethasone prevented an elevation in ABR thresholds at all frequencies compared with the control group (8 - 32 kHz) at 1 and 4 weeks post implantation. This protection was not seen with a lower dose (0.2mg/kg) of dexamethasone. There was a foreign body reaction observed in control and low-dose treated animals, however this was suppressed in all but one of the high-dose dexamethasone-treated animals. Conclusions: Intravenous high dose dexamethasone protects hearing during cochlear implantation and prevents the development of an inflammatory histological response. The prolonged intra-operative delay required for local delivery is avoided in this model. Furthermore, it may provide better protection of low frequency hearing than locally administered steroid.
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ItemEffects of chronic electrical stimulation and exogenous neurotrophins in the deafened cochlea( 2011)The loss of cochlear hair cells is a common cause of deafness. Auditory perception can be restored to some deaf patients using a cochlear implant, which electrically stimulates the spiral ganglion neurons (SGN) of the auditory nerve. In the normal cochlea, hair cells produce peptides called neurotrophins which provide a pro-survival signal to the SGNs. The loss of hair cells can therefore result in the degeneration of SGNs, which could potentially affect implant performance. The application of exogenous neurotrophins to the cochlear fluid can prevent SGN degeneration and may induce the formation of new neurons (neurogenesis), as suggested by the results of some studies. Neurotrophin treatment may also promote the ectopic regrowth of SGN peripheral processes. The cochlear implant relies in part upon the orderly spatial organisation of SGNs to impart pitch information. Therefore, the disorganised process regrowth seen following neurotrophin treatment could degrade implant performance. Furthermore, the morphology of SGN peripheral processes has not been studied following the combined application of neurotrophins and chronic intracochlear electrical stimulation (ICES). This is an important treatment combination to investigate for the clinical advancement of intracochlear neurotrophin use. This study aimed to describe the effects of neurotrophin and/or ICES treatment on several aspects of SGN biology, with the primary emphasis on the potential relationship between SGN process disorganisation and the spatial selectivity of ICES. Ototoxically deafened guinea pigs were treated with neurotrophins and/or chronic ICES for the following studies: • The ectopic growth of peripheral processes was quantified using single SGN peripheral process tracings. It was found that SGN process disorganisation was significantly increased following neurotrophin treatment, and that ICES had no effect. • The spatial selectivity of ICES was measured by recording the spread of activation in the auditory midbrain. Neurotrophin treatment did not affect the spread of midbrain activation, whereas chronic ICES produced increased spread, as well as decreased the depth of electrode tuning – another indication of degraded spatial selectivity. However, neurotrophins did reduce the activation threshold to ICES.• The potential induction of SGN neurogenesis was investigated using a marker for DNA synthesis. However, no evidence of neurogenesis was seen.• Finally, SGN peripheral processes were examined using electron microscopy to determine if ultrastructural changes were caused by the treatments. Some key observations were that peripheral process degeneration tended to precede myelin degeneration, neurotrophins reduced the extent of peripheral process shrinkage caused by deafness, and chronic ICES caused further process shrinkage. In summary, this study has demonstrated that neurotrophin treatment causes functional and anatomical changes that may be beneficial to cochlear implant patients. The potential problem of increased peripheral process disorganisation seems to be of little functional consequence with regards to spatial selectivity, likely due to the small scale of process disorganisation compared to the electrical current pathways produced by ICES.