TNF-α inhibition using etanercept prevents noise-induced hearing loss by improvement of cochlear blood flow in vivo

被引:57
作者
Arpornchayanon, Warangkana [1 ,2 ]
Canis, Martin [1 ,3 ]
Ihler, Friedrich [1 ,3 ]
Settevendemie, Claudia [4 ]
Strieth, Sebastian [1 ,4 ]
机构
[1] Univ Munich LMU, Walter Brendel Ctr Expt Med WBex, Munich, Germany
[2] Chiang Mai Univ, Fac Med, Dept Pharmacol, Chiang Mai, Thailand
[3] Univ Gottingen, Dept Otorhinolaryngol, Gottingen, Germany
[4] Goethe Univ Frankfurt, Dept Otorhinolaryngol, D-60590 Frankfurt, Germany
关键词
Microcirculation; NIHL; etanercept; stria vascularis; intravital microscopy; NECROSIS-FACTOR-ALPHA; GUINEA-PIG COCHLEA; ACOUSTIC TRAUMA; VELOCITY; MICROCIRCULATION; CAPILLARIES; RECRUITMENT; EXPRESSION; EXPOSURE; THERAPY;
D O I
10.3109/14992027.2013.790564
中图分类号
R36 [病理学]; R76 [耳鼻咽喉科学];
学科分类号
100104 ; 100213 ;
摘要
Objective: Exposure to loud noise can impair cochlear microcirculation and cause noise-induced hearing loss (NIHL). TNF-alpha signaling has been shown to be activated in NIHL and to control spiral modiolar artery vasoconstriction that regulates cochlear microcirculation. It was the aim of this experimental study to analyse the effects of the TNF-alpha inhibitor etanercept on cochlear microcirculation and hearing threshold shift in NIHL in vivo. Design: After assessment of normacusis using ABR, loud noise (106 dB SPL, 30 minutes) was applied on both ears in guinea pigs. Etanercept was administered systemically after loud noise exposure while control animals received a saline solution. In vivo fluorescence microscopy of strial capillaries was performed after surgical exposure of the cochlea for microcirculatory analysis. ABR measurements were derived from the contralateral ear. Study sample: Guinea pigs (n=6, per group). Results: Compared to controls, cochlear blood flow in strial capillary segments was significantly increased in etanercept-treated animals. Additionally, hearing threshold was preserved in animals receiving the TNF-alpha inhibitor in contrast to a significant threshold raising in controls. Conclusions: TNF-alpha inhibition using etanercept improves cochlear microcirculation and protects hearing levels after loud noise exposure and appears as a promising treatment strategy for human NIHL.
引用
收藏
页码:545 / 552
页数:8
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