G Bredberg

Karolinska Institutet, Solna, Stockholm, Sweden

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Publications (22)26.21 Total impact

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    ABSTRACT: Based on in vitro studies, it is hypothesized that neurotrophic factor deprivation following deafferentation elicits an oxidative state change in the deafferented neuron and the formation of free radicals that then signal cell death pathways. This pathway to cell death was tested in vivo by assessing the efficacy of antioxidants (AOs) to prevent degeneration of deafferented CNVIII spiral ganglion cells (SGCs) in deafened guinea pigs. Following destruction of sensory cells, guinea pigs were treated immediately with Trolox (a water soluble vitamin E analogue)+ascorbic acid (vitamin C) administered either locally, directly in the inner ear, or systemically. Electrical auditory brainstem response (EABR) thresholds were recorded to assess nerve function and showed a large increase following deafness. In treated animals EABR thresholds decreased and surviving SGCs were increased significantly compared to untreated animals. These results indicate that a change in oxidative state following deafferentation plays a role in nerve cell death and antioxidant therapy may rescue SGCs from deafferentation-induced degeneration.
    Neurobiology of Disease 03/2007; 25(2):309-18. · 5.62 Impact Factor
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    ABSTRACT: Benefits of cochlear prostheses for the deaf are dependent on survival and excitability of the auditory nerve. Degeneration of deafferented auditory nerve fibers is prevented and excitability maintained by immediate replacement therapy with exogenous neurotrophic factors, in vivo. It is important to know whether such interventions are effective after a delay following deafness, typical for the human situation. This study evaluated the efficacy of brain-derived neurotrophic factor (BDNF) and ciliary neurotrophic factor axokine-1 analogue (CNTF Ax1) application, 2 or 6 weeks postdeafening, in preventing further degeneration and a decrease in excitability. Guinea pigs were deafened and implanted with intracochlear stimulating electrodes, a scala tympani cannula-osmotic pump system, and auditory brainstem response (ABR) recording electrodes. Subjects received BDNF + CNTF Ax1 or artificial perilymph (AP) treatment for 27 days, beginning at 2 or 6 weeks following deafening. Electrical (E) ABR thresholds increased following deafening. After 1 week, in the 2-weeks-delayed neurotrophic factor treatment group, EABR thresholds decreased relative to AP controls, which were statistically significant at 2 weeks. In the 6-week delay group, a tendency to enhanced EABR sensitivity began at 2 weeks of treatment and increased thereafter, with a significant difference between neurotrophic factor- and AP-treated groups across the treatment period. A clear, statistically significant, enhanced survival of spiral ganglion cells was seen in both neurotrophic factor treatment groups relative to AP controls. These findings demonstrate that BDNF + CNTF Ax1 can act to delay or possibly even reverse degenerative and, likely apoptotic, processes well after they have been activated. These survival factors can rescue cells from death and enhance electrical excitability, even during the period of degeneration and cell loss when the spiral ganglion cell population is reduced by >50% (6 weeks). It is noteworthy that this same degree of ganglion cell loss, secondary to receptor damage, is typically observed after a period equivalent to some years of deafness in humans.
    Journal of Neuroscience Research 10/2004; 78(1):75-86. · 2.97 Impact Factor
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    ABSTRACT: This study describes open-set speech recognition in cochlear implant subjects with ossified cochleae and compares it to a control group with open cochleae. Twenty-one postlingually deafened adults with a Med-El Combi 40/40+GB split- electrode implant were matched to patients using a Med-El cochlear implant with a standard electrode. Speech recognition was assessed over an 18-month period. Split- electrode patients improved significantly over time, but their scores were significantly lower and increased significantly slower than those of controls. Of 14 patients with a duration of deafness less than 20 years, average sentence test scores were 50%, and average monosyllabic word test scores were 31%. This study provides evidence that cochlear implantation is beneficial to patients with ossified cochleae, but early implantation is advisable.
    Cochlear Implants International 07/2003; 4(2):55-72.
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    ABSTRACT: A primary cause of deafness is damage of receptor cells in the inner ear. Clinically, it has been demonstrated that effective functionality can be provided by electrical stimulation of the auditory nerve, thus bypassing damaged receptor cells. However, subsequent to sensory cell loss there is a secondary degeneration of the afferent nerve fibers, resulting in reduced effectiveness of such cochlear prostheses. The effects of neurotrophic factors were tested in a guinea pig cochlear prosthesis model. After chemical deafening to mimic the clinical situation, the neurotrophic factors brain-derived neurotrophic factor and an analogue of ciliary neurotrophic factor were infused directly into the cochlea of the inner ear for 26 days by using an osmotic pump system. An electrode introduced into the cochlea was used to elicit auditory responses just as in patients implanted with cochlear prostheses. Intervention with brain-derived neurotrophic factor and the ciliary neurotrophic factor analogue not only increased the survival of auditory spiral ganglion neurons, but significantly enhanced the functional responsiveness of the auditory system as measured by using electrically evoked auditory brainstem responses. This demonstration that neurotrophin intervention enhances threshold sensitivity within the auditory system will have great clinical importance for the treatment of deaf patients with cochlear prostheses. The findings have direct implications for the enhancement of responsiveness in deafferented peripheral nerves.
    Proceedings of the National Academy of Sciences 03/2002; 99(3):1657-60. · 9.74 Impact Factor
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    ABSTRACT: Pneumococcal otogenic meningitis is a rare postsurgical complication that can develop following stapedectomy or after cochlear implantation. The bacterial infection can be fatal in some instances. A recent increase in the incidence of otogenic meningitis among cochlear implant wearers is of concern. The majority of meningitis cases are associated with a 2-component electrode manufactured by one cochlear implant company. The device with the added 'positioner' component has been withdrawn from the market (FDA Public Health Web Notification: Cochlear Implant Recipients may be at Greater Risk for Meningitis, Updated: August 29, 2002, www.fda.gov/cdrh/safety/cochlear.html). Not all cases have been subsequent to otitis media and symptoms have developed from less than 24 h up to a few years after implantation. The purpose of this paper is to review and discuss the pathogenesis, pathology/bacteriology and to elaborate on some clinical features of otogenic meningitis in implanted children and adults. Essential aspects of surgery, electrode design, and cochleostomy seal are discussed. Conclusions are drawn from the available data and recommendations are made for good practice in cochlear implantation and follow-up.
    ORL 01/2002; 64(6):382-9. · 1.10 Impact Factor
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    ABSTRACT: Children with CHARGE have multiple disabilities. Impairments of vision and hearing, balance problems and facial palsy are common. Few reports have dealt with their radiological temporal bone changes and none with cochlear implant surgery. The pre-operative temporal bone computed tomography (CT) and surgical findings of one child with CHARGE and one with a CHARGE-like condition who have received cochlear implants are reported. The findings include absent semicircular canals, narrow orifice for the cochlear nerve, and abnormalities of the oval and round window, the facial canal and the ossicles. CT can be used as a diagnostic tool as these combinations of temporal bone changes are extremely rare in other materials. Cochlear implants may help these often very isolated children to communicate. Copyright © 2001 Whurr Publishers Ltd.
    Cochlear Implants International 02/2001; 2(1):59 - 71.
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    ABSTRACT: The effects of obliteration of the mastoid cavity on the growth of residual cholesteatoma were histologically studied in an animal model. A dermal cyst was produced by grafting a piece of autologous auricular skin in the otic bulla of 11 guinea-pigs. Three weeks after grafting, part of the cyst wall facing the cavity was removed and the debris accumulated inside was inserted into the surrounding granulation using a micropick. This procedure simulates the growth mechanism of cholesteatoma residue which sometimes occurs after middle ear surgery in human subjects. In six animals, the bulla was then obliterated with plaster of Paris. The remaining five animals were used as controls. Animals were killed for histological study at 2, 4 or 8 weeks postoperatively. Microscopic examinations revealed that in the obliteration group, severe inflammatory reactions were induced in the otic bulla, although the graft epithelium survived there; dermal cyst reformed in only one of six animals. In the controls, cyst reformation was recognized in all animals. This indicated that severe inflammation induced by plaster prevented growth of the graft epithelium in the otic bulla.
    Acta Oto-Laryngologica 01/1998; 118(1):101-4. · 1.11 Impact Factor
  • The American journal of otology 12/1997; 18(6 Suppl):S42-3.
  • G Linde, G Bredberg, B Lindström
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    ABSTRACT: To evaluate the effectiveness of the Nucleus 20 + 2 implant in a group of patients. Fifteen children and 11 adults who have received the Nucleus 20 + 2 implant since late 1993. The outcome in most patients has been favorable.
    The American journal of otology 12/1997; 18(6 Suppl):S149-50.
  • B Lindström, G Bredberg
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    ABSTRACT: To describe the use of intraoperative electrical stimulation on the stapedius reflex in children. Hospital cochlear implantation center. Eighteen children under the age of 10 years, who have undergone cochlear implantation, have been examined during surgery with the electrically elicited stapedius reflex in the monopolar stimulation mode. A stapedius reflex could visually be detected for all subjects. The responses serve to test the implant, provide guidance in avoiding overstimulation of the child when the device is switched on, and estimate the optimal C-levels.
    The American journal of otology 12/1997; 18(6 Suppl):S118-9.
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    ABSTRACT: The inner ear toxicity of ionomeric cement (Ionocem) when used as a reconstructive material in ear surgery was evaluated in 47 guinea pigs used in a morphological study. The cement was implanted on either the promontory, the round window membrane or the stapes. There was no significant hair cell loss compared with the control ear at three weeks, two months or three months after implantation. Using electrocochleography, the hearing thresholds before, and three weeks, two and three months after the implantation were compared in an additional seven animals. No evident hearing loss was observed in any animal during the study period. No morphological or functional evidence for an ototoxic effect of the ionomeric cement was found in this study.
    Ear, nose, & throat journal 05/1997; 76(4):223-6, 228, 230. · 1.03 Impact Factor
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    ABSTRACT: A model of auditory performance and a model of ganglion cell survival in postlinguistically deafened adult cochlear implant users are suggested to describe the effects of aetiology, duration of deafness, age at implantation, age at onset of deafness, and duration of implant use. The models were compared with published data and a composite data set including 808 implant users. Qualitative agreement with the model of auditory performance was found. Duration of deafness had a strong negative effect on performance. Age at implantation had a slight negative effect on performance, increasing after age 60 years. Age at onset of deafness had little effect on performance up to age 60. Duration of implant use had a positive effect on performance. Aetiology had a relatively weak effect on performance.
    Audiology and Neurotology 01/1996; 1(5):293-306. · 2.32 Impact Factor
  • The Annals of otology, rhinology & laryngology. Supplement 10/1995; 166:287-90.
  • G Bredberg, B Lindström
    The Annals of otology, rhinology & laryngology. Supplement 10/1995; 166:256-8.
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    ABSTRACT: Electromagnetically induced auditory perception was investigated in 18 deaf patients who were candidates for cochlear implants. In the extracranial magnetic stimulation (EMS) procedure, patients were stimulated with time-varying magnetic field brief pulses from a coil positioned at the i) auricle, ii) the mastoid, and iii) the temporal lobe area. EMS elicited auditory sensations in 26 ears (of 14 patients/subjects). The lowest threshold of auditory sensation (TAS) was found to be at the 20% EMS level, with a range of 20-50% of the maximum level (2.0 Tesla), and approximately equal sensitivity in each coil position. Eleven of the subjects hearing EMS-induced sound perceived changes in pitch while 6 heard "clicks" or clicks and tones. Spearman Rho correlation analysis showed a mild negative correlation between the EMS/TAS and the pre-implant FFA, best tone threshold (BTT), and direct promontorial electrical stimulation (ES) thresholds at 250 Hz and 500 Hz. No correlation was found between EMS or ES and performance on the pre-implant or post-implant psychacoustic tests (MAC VIII or 3-Digit speech tests) or the measurements of the thickness of cutaneous and osseous tissue from the stimulation sites at the mastoid and ear canal to the cochlear and 8th nerve. A fair positive correlation was found between the EMS/TAS and the post-implant (6 months) ES threshold when the electrodes allocated the 500 Hz frequency range were stimulated. A mild positive correlation between the pre-cochlear-implant promontorial electrical stimulation (ES) at 250 Hz and the four frequency tone average (FFA: 0.5, 1, 2, 4 kHz) was also found.(ABSTRACT TRUNCATED AT 250 WORDS)
    Acta Oto-Laryngologica 10/1994; 114(5):501-9. · 1.11 Impact Factor
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    ABSTRACT: Cochlear blood flow (CBF) was measured with a laser-Doppler (L-D) flowmeter (Periflux PR2-B) in four unanesthetized human subjects with chronic tympanic membrane perforations and nine anesthetized human subjects undergoing middle ear operations. The L-D recordings were made over the promontory and/or the round window membrane during carbogen breathing and direct electrical stimulation of the cochlea in both groups and with warm water irrigation of the external ear canal in the anesthetized subjects. Carbogen led to little or no change in CBF as monitored with either measurement approach in either subject group. Electrical stimulation yielded an increase (15% to 25%) in CBF as recorded from the promontory in seven of the nine subjects tested. Warm (44 degrees C to 49 degrees C) water irrigation produced changes of 20% to 60% in CBF that were partially recoverable in the 10 minutes available for study. This study demonstrated the feasibility of direct CBF measurement in humans with the L-D method. Moreover, the data indicate that carbogen has little influence on CBF and that electrical stimulation at relatively safe levels and warm water irrigation of the ear canal produce increases in human CBF.
    The Annals of otology, rhinology, and laryngology 02/1991; 100(1):44-53. · 1.21 Impact Factor
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    ABSTRACT: It has been difficult to explain the good speech understanding obtained by some cochlear implant patients fitted with a single-channel electrode and analog transmissions of the speech signal (Vienna/3M implant). It has also been difficult to explain the variation in results reported by different groups using the same implant. One hypothesis asserts that the above differences can be explained by the observation that electric stimulation with an implanted electrode might result in two different auditory sensations, the first resulting from the stimulation of the remaining hair cells (electrophonic component) and the second from the electric stimulation of the auditory nerve (electro-neural component). The two sensations are very different. As a result of different definitions of total deafness (functional or threshold definition), patients with remaining hair cells are operated on by some groups, but not by other groups. Some published results from different studies are discussed with reference to the above hypothesis and the possible consequences for the selection of the patients, the use of extra- or intracochlear electrodes, and the selection of the speech coding strategy are discussed.
    Acta oto-laryngologica. Supplementum 02/1990; 469:156-63.
  • Scandinavian audiology. Supplementum 02/1983; 18:11-21.
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    ABSTRACT: The analyses have given some general clues to the therapeutic handling of these patient categories: 1. The A and B groups can be labelled "hearing" with clearly useful residual hearing. 2. The patients in the C group, as a rule, are utilizing very little from acoustic speech stimulation, mostly the prosodic information. Several patients in this group are possible implant candidates, and it is reasonable to expect that (with a suitable stimulus device and a suitable application of this) the patients could get an additional support during speech reading, so that they function as the B group. Tactile devices are also an alternative or a supplement for this group, and a pilot study on six patients is in progress in the department in cooperation with the Department of Speech Communication at the Royal Institute of Technology. 3. The patients within the A and B groups will in the first place be offered additional functional training programmes (prosodic training, audio-visual training and possibly vibration training) and, as an ultimate alternative a social activation in group therapy may be considered. Some patients in these groups might also be candidates in the future for an extra cochlear implant.
    Scandinavian audiology. Supplementum 02/1983; 18:33-44.
  • B Grubbström, G Bredberg, T Lundborg
    Scandinavian audiology. Supplementum 02/1983; 18:23-31.

Publication Stats

327 Citations
26.21 Total Impact Points

Institutions

  • 1997–2004
    • Karolinska Institutet
      • • Institutionen för klinisk neurovetenskap
      • • Division of Audiology
      Solna, Stockholm, Sweden
  • 2001–2003
    • Akademiska Sjukhuset
      Uppsala, Uppsala, Sweden
  • 1990
    • KTH Royal Institute of Technology
      Tukholma, Stockholm, Sweden