Tumor Necrosis Factor-induced Decrease of Cochlear Blood Flow Can Be Reversed by Etanercept or JTE-013.
Otol Neurotol
; 37(7): e203-8, 2016 08.
Article
em En
| MEDLINE
| ID: mdl-27295443
ABSTRACT
HYPOTHESIS:
This study aimed to quantify the effects of tumor necrosis factor (TNF) inhibitor Etanercept and sphingosine-1-phosphate receptor 2 antagonist JTE-013 on cochlear blood flow in guinea pigs after TNF-induced decrease.BACKGROUND:
Sudden sensorineural hearing loss is a common cause for disability and reduced quality of life. Good understanding of the pathophysiology and strong evidence-based therapy concepts are still missing. In various inner ear disorders, inflammation and impairment of cochlear blood flow (CBF) have been considered factors in the pathophysiology. A central mediator of inflammation and microcirculation in the cochlea is TNF. S1P acts downstream in one TNF pathway.METHODS:
Cochlea lateral wall vessels were exposed surgically and assessed by intravital microscopy in guinea pigs in vivo. Twenty-eight animals were randomly distributed into four groups of seven each. Exposed vessels were superfused by TNF (5.0âng/ml) and afterward repeatedly either by Etanercept (1.0âµg/ml), JTE-013 (10âµmol/L), or vehicle (0.9 % NaCl solution or ethanol phosphate-buffered saline buffer, respectively).RESULTS:
After decreasing CBF with TNF (pâ<0.001, two-way RM ANOVA), both treatments reversed CBF, compared with vehicle (pâ<0.001, two-way RM ANOVA). The comparison of the vehicle groups showed no difference (pâ=â0.969, two-way RM ANOVA), while there was also no difference between the treatment groups (pâ=â0.850, two-way RM ANOVA).CONCLUSION:
Both Etanercept and JTE-013 reverse the decreasing effect of TNF on cochlear blood flow and, therefore, TNF and the S1P-signalling pathway might be targets for treatment of microcirculation-related hearing loss.
Texto completo:
1
Coleções:
01-internacional
Temas:
Geral
/
Prevencao_e_fatores_de_risco
/
Alcoolismo
Base de dados:
MEDLINE
Assunto principal:
Pirazóis
/
Piridinas
/
Fator de Necrose Tumoral alfa
/
Cóclea
/
Etanercepte
/
Imunossupressores
Tipo de estudo:
Etiology_studies
/
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Otol Neurotol
Assunto da revista:
NEUROLOGIA
/
OTORRINOLARINGOLOGIA
Ano de publicação:
2016
Tipo de documento:
Article
País de afiliação:
Alemanha