Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow

Bertlich, Mattis; Ihler, Friedrich; Weiss, Bernhard G.; Freytag, Saskia; Jakob, Mark; Strupp, Michael; Pellkofer, Hannah; Canis, Martin

doi:10.1097/mao.0000000000001510

Cited by 4 publications

(6 citation statements)

References 28 publications

(51 reference statements)

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“…Consequently, it has been shown that cochlear microcirculation may actually recover from TNF-induced decreases by application of JTE-013, FTY-720, or etanercept. 22,45 In conclusion, we were able to prove that LPS decreases cochlear microcirculation in a dose-dependent manner. Moreover, this effect is at least in parts mediated by the TNF pathway.…”

Section: Independent Of How High the Concentration Of Lps Was Appliedmentioning

confidence: 57%

“…Hence, etanercept is a viable candidate for clinical treatment of otitis media with suppurative labyrinthitis, even if a recent shift in hearing threshold has already been diagnosed. Consequently, it has been shown that cochlear microcirculation may actually recover from TNF‐induced decreases by application of JTE‐013, FTY‐720, or etanercept 22,45 …”

Section: Discussion/conclusionmentioning

confidence: 99%

“…The animal model used has been described 20 and used 16,[21][22][23] extensively. Anesthesia was induced by intramuscular injection of 85 mg/ kg bodyweight (b.w.)…”

Section: Anesthesia and Surgical Preparationmentioning

confidence: 99%

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Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

et al. 2021

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Acute otitis media is one of the most common infectious diseases, affecting up to 11% of the worldwide population, reflecting between 300 and 700 million patients per year. 1 About half the patients affected are children, 1 and otitis media (including its chronic forms) is responsible for up to 3.200 deaths per year. 2 About 140 million patients retain a hearing impairment after acute otitis media each year, which can be caused by persisting perforation of the tympanic membrane or suppurative labyrinthitis and subsequent sensorineural hearing loss. 3

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Section: Independent Of How High the Concentration Of Lps Was Appliedmentioning

confidence: 57%

Section: Discussion/conclusionmentioning

confidence: 99%

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Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

et al. 2021

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“…This animal model has repeatedly been used to address numerous question in relation with cochlear microcirculation (20)(21)(22). Anesthesia was induced by a single injection of ketamin/xylazine (85 mg/kg and 8.5 mg/kg bodyweight, respectively) and kept up by repeated injection of half the above dose every 30 minutes.…”

Section: Anesthesia and Surgical Preparationmentioning

confidence: 99%

Cannabinoid Receptor 2 Agonism is Capable of Preventing Lipopolysaccharide Induced Decreases of Cochlear Microcirculation – A Potential Approach for Inner Ear Pathologies

Weiss

Freytag

Kloos³

et al. 2021

Otology &Amp; Neurotology

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Hypothesis:The ability of JWH-133, an agonist at the cannabinoid receptor 2, to abrogate the effects of lipopolysaccharide on cochlear microcirculation was investigated. Background: Cochlear inflammation and subsequent impairment of microcirculation is part of numerous pathologies affecting inner ear function, including suppurative labyrinthitis, noise trauma, and sudden sensorineural hearing loss. One way of causing cochlear inflammation is exposing the cochlea to lipopolysaccharide, a bacterial endotoxin. Methods: Twenty Dunkin-hartley guinea pigs were divided into four groups of five animals each. Two groups received topic treatment with JWH-133 and two received treatment with placebo. One group that had been treated with JWH-133 and one with placebo were then exposed to lipopolysaccharide or placebo, respectively. Cochlear microcirculation was quantified before, in between and after treatments by in vivo fluorescence microscopy. Results: Significantly different changes in cochlear blood flow were only seen in the group that was treated with placebo and subsequently lipopolysaccharide. Every other group showed no significant change in cochlear blood flow. Conclusion: JWH-133 is capable of abrogating the effects of lipopolysaccharide on cochlear microcirculation. It may therefore be clinical interest in treating numerous inflammation associated cochlear pathologies.

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“…elektrischen Signalen durch die Haarzellen nicht mehr möglich ist (Thalmann et al 1972;Konishi 1979). Auch die An-- und Abwesenheit von Zytokinen wie beispiels-weise dem Tumornekrosefaktor--α nimmt über Vermittlung von weiteren Signal-kaskaden Einfluss auf den cochleären Blutfluss (Scherer et al 2010;Bertlich et al 2017).…”

Section: Das Hörvermögen In Abhängigkeit Vom Cochleären Blutflussunclassified

Methylprednisolon zur Behandlung des akuten Hörverlusts im Tiermodell: Eine doppelblinde placebokontrollierte Studie

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Fingolimod (FTY-720) is Capable of Reversing Tumor Necrosis Factor Induced Decreases in Cochlear Blood Flow

Abstract: FTY-720 is capable of reversing changes in cochlear blood flow induced by application of TNF. This makes FTY-720 a valid candidate for potential treatment of numerous inner ear pathologies.

Cited by 4 publications

References 28 publications

Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

Lipopolysaccharide decreases cochlear blood flow dose dependently in a guinea pig animal model via TNF signaling

Cannabinoid Receptor 2 Agonism is Capable of Preventing Lipopolysaccharide Induced Decreases of Cochlear Microcirculation – A Potential Approach for Inner Ear Pathologies

Methylprednisolon zur Behandlung des akuten Hörverlusts im Tiermodell: Eine doppelblinde placebokontrollierte Studie

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