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BDNF as otoprotectant in toxin-induced hearing loss
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Surgical Sciences, Otolaryngology and Head and Neck Surgery.
2013 (English)In: Acta Oto-Laryngologica, ISSN 0001-6489, E-ISSN 1651-2251, Vol. 133, no 1, 4-11 p.Article in journal (Refereed) Published
Abstract [en]

Conclusion: Brain-derived neurotrophic factor (BDNF) can prevent auditory brainstem response (ABR) threshold shift changes caused by Pseudomonas aeruginosa exotoxin A (PaExoA). Objective: Peptides of the neurotrophin family are known to prevent neuronal death during embryonic development by interacting with specific membrane receptors. The purpose of this study was to investigate whether a single dose of BDNF is an effective protectant against toxic effects of PaExoA-induced ABR threshold shifts. Materials and Methods: Eight groups of Sprague-Dawley rats were used. There were five control groups (n = 20) as follows. Group A (n = 4) received NaCl solution; group B (n = 3) received 4 mu g BDNF; group C (n = 4) received 1 mu g/20 mu l PaExoA; group D (n = 4) received 2 mu g/20 mu l PaExoA; groupE (n = 5) received 10 mu g/20 mu l PaExoA injected into the round window niche. Three treatment groups (n = 13) received a single dose of PaExoA and 4 mu g of BDNF simultaneously. Group 1 (n = 3) received 1 mu g/20 mu l PaExoA + 4 mu g of BDNF; group 2 (n = 5) received 2 mu g/20 mu l PaExoA + 4 mg BDNF; group 3 (n = 5) received 10 mu g/20 mu l PaExoA+ 4 mu g BDNF. ABR was used to measure efficacy by analyzing threshold shifts before and after injections. Results: A single dose of BDNF prevented changes in ABR thresholds following exposure to increasing concentrations of PaExoA injected into the middle ear.

Place, publisher, year, edition, pages
2013. Vol. 133, no 1, 4-11 p.
Keyword [en]
Auditory brainstem response, Brain-derived neurotrophic factor, Pseudomonas aeruginosa exotoxin A, cochlea, round window membrane, rat
National Category
Medical and Health Sciences
Identifiers
URN: urn:nbn:se:uu:diva-192429DOI: 10.3109/00016489.2012.712216ISI: 000312525800001OAI: oai:DiVA.org:uu-192429DiVA: diva2:600369
Available from: 2013-01-24 Created: 2013-01-21 Last updated: 2017-12-06Bibliographically approved
In thesis
1. Time-related Aspects of Otoprotection: Experimental Studies in Rat
Open this publication in new window or tab >>Time-related Aspects of Otoprotection: Experimental Studies in Rat
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Intratympanic injection of various otoprotectants through the round window membrane (RWM) might become available in the near future as an alternative to the currently available medical and surgical methods used to treat several inner ear diseases. The most common outcome of such diseases is sensorineural hearing loss (SNHL).

Two examples of  these otoprotectants are Edaravone and Brain-Derived Neurotrophic Factor (BDNF), both of which have already proved effective against  noise-induced hair cell loss, barotrauma  and ototoxicity caused by cisplatin. In four different studies we used two electrophysiological methods, auditory brainstem response (ABR) and distortion product otoacoustic emission (DPOAE), to study the effects of tobramycin and Pseudomonas aeruginosa exotoxin A (PaExoA) on the inner ears of 129 male Sprague-Dawley rats.

In two investigations, not only the otoprotective effects of Edaravone on tobramycin-induced ABR threshold shifts and PaExoA-induced DPOAE  threshold changes, were studied but even different application times, in order to establish in which interval it was still possible to achieve effective otoprotection.We found that Edaravone gave otoprotection from tobramycin when injected simultaneously or within 7 days, but it had only a limited effect on the changes in DPOAE thresholds caused by PaExoA when injected 1, 2, or 4 hours after the exotoxin.

The effect of BDNF on PaExoA-induced ABR threshold shifts was investigated in two studies, where different doses of intratympanically injected PaExoA were used and where BDNF was applied simultaneously, 12 or 72 hours efter exotoxin instillation. We found that BDNF had an otoprotective effect on SNHL induced by different doses PaExoA when injected simultaneously or with no more than 12 hours delay.

 

Place, publisher, year, edition, pages
Uppsala: Acta Universitatis Upsaliensis, 2013. 49 p.
Series
Digital Comprehensive Summaries of Uppsala Dissertations from the Faculty of Medicine, ISSN 1651-6206 ; 901
Keyword
sensorineural hearing loss, Edaravone, brain-derived neurotrophic factor, auditory brainstem response, Sprague-Dawley rat, distortion product otoacoustic emission, Pseudomonas aeruginosa exotoxin A.
National Category
Medical and Health Sciences
Research subject
Oto-Rhino-Laryngology
Identifiers
urn:nbn:se:uu:diva-198450 (URN)978-91-554-8661-7 (ISBN)
Public defence
2013-06-13, Skoogsalen, Akademiska sjukhuset (ingång 78-79), Uppsala, 09:15 (Swedish)
Opponent
Supervisors
Available from: 2013-05-22 Created: 2013-04-15 Last updated: 2013-08-30

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Lidian, AdnanLinder, BirgittaAnniko, MattiNordang, Leif

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