耳鼻咽喉科・頭頸部外科87巻8号

2015年07月発行

特集① 突発性難聴とその周辺疾患

突発性難聴の病態

著者： 松永達雄¹ 瀧口洋一郎²

所属機関： ¹国立病院機構東京医療センター感覚器センター・臨床遺伝センター ²永寿総合病院耳鼻咽喉科

ページ範囲：P.564 - P.572

文献概要

POINT

●突発性難聴の病態として循環障害説とウイルス感染説が有力な説とされてきた。

●近年ストレス応答説が提唱されており，新たな病態論として注目が集まっている。

●内耳ミトコンドリアの急性障害による突発性難聴動物モデル（急性内耳エネルギー不全モデル）では蝸牛線維細胞の障害が主たる病態であり，組織再生と可塑的変化が続く。

●難聴発症には小胞体ストレス，カスパーゼ経路アポトーシス，炎症性サイトカイン・ケモカインなどが関与する。

●蝸牛線維細胞の変性に対して骨髄間葉系幹細胞移植，シャペロン分子リガンドの効果が認められる。

参考文献

1）Lin HC, et al：Sudden sensorineural hearing loss increases the risk of stroke：a 5-year follow-up study. Stroke 39：2744-2748, 2008

2）Ogawa K, et al：Effect of prostaglandin E1 on idiopathic sudden sensorineural hearing loss：a double-blinded clinical study. Otol Neurotol 23：665-668, 2002

3）Yoshida T, et al：Three-dimensional fluid-attenuated inversion recovery magnetic resonance imaging findings and prognosis in sudden sensorineural hearing loss. Laryngoscope 118：1433-1437, 2008

4）Wu X, et al：Magnetic resonance imaging-detected inner ear hemorrhage as a potential cause of sudden sensorineural hearing loss. Am J Otolaryngol 35：318-323, 2014

5）Kimura RS：Animal models of inner ear vascular disturbances. Am J Otolaryngol 7：130-139, 1986

6）暁　清文：虚血性内耳病変の発症機序と臨床．第108回日本耳鼻咽喉学会宿題報告モノグラフ，佐川印刷，愛媛，2007

7）Vasama JP, et al：Idiopathic sudden sensorineural hearing loss：temporal bone histopathologic study. Ann Otol Rhinol Laryngol 109：527-532, 2000

8）Linthicum FH, et al：Idiopathic sudden sensorineural hearing loss：vascular or viral? Otolaryngol Head Neck Surg 149：914-917, 2013

9）Schuknecht HF, et al：The pathology of sudden deafness. Acta Otolaryngol 76：75-97, 1973

10）Fukuda S, et al：An anti-mumps IgM antibody level in the serum of idiopathic sudden sensorineural hearing loss. Auris Nasus Larynx 28：S3-5, 2001

11）Kikidis D, et al：Sudden sensorineural hearing loss：subclinical viral and toxoplasmosis infections as aetiology and how they alter the clinical course. ORL J Otorhinolaryngol Relat Spec 73：110-115, 2011

12）Merchant SN, et al：Sudden deafness：is it viral? ORL J Otorhinolaryngol Relat Spec 70：52-60, 2008

13）Adams JC：Clinical implications of inflammatory cytokines in the cochlea：a technical note. Otol Neurotol 23：316-322, 2002

14）Merchant SN, et al：Pathology and pathophysiology of idiopathic sudden sensorineural hearing loss. Otol Neurotol 26：151-160, 2005

15）Masuda M, et al：Correlations of inflammatory biomarkers with the onset and prognosis of idiopathic sudden sensorineural hearing loss. Otol Neurotol 33：1142-1150, 2012

16）松永達雄：感覚器の再生医療—蝸牛線維細胞を標的とした感音難聴の再生治療．医学のあゆみ226：986-990，2008

17）Mizutari K, et al：Balance dysfunction resulting from acute inner ear energy failure is caused primarily by vestibular hair cell damage. J Neurosci Res 88：1262-1272, 2010

18）Mizutari K, et al：Late-phase recovery in the cochlear lateral wall following severe degeneration by acute energy failure. Brain Res 1419：1-11, 2011

19）Takiguchi Y, et al：Long-lasting changes in the cochlear K＋ recycling structures after acute energy failure. Neurosci Res 77：33-41, 2013

20）Mutai H, et al：Mitotic activity and specification of fibrocyte subtypes in the developing rat cochlear lateral wall. Neuroscience 163：1255-1263, 2009

21）Fujinami Y, et al：Enhanced expression of C/EBP homologous protein（CHOP）precedes degeneration of fibrocytes in the lateral wall after acute cochlear mitochondrial dysfunction induced by 3-nitropropionic acid. Neurochem Int 56：487-494, 2010

22）Fujinami Y, et al：A novel animal model of hearing loss caused by acute endoplasmic reticulum stress in the cochlea. J Pharmacol Sci 118：363-372, 2012

23）Fujioka M, et al：Pharmacological inhibition of cochlear mitochondrial respiratory chain induces secondary inflammation in the lateral wall：a potential therapeutic target for sensorineural hearing loss. PLoS One 9：e90089, 2014

24）Sun GW, et al：Functional interaction between mesenchymal stem cells and spiral ligament fibrocytes. J Neurosci Res 90：1713-1722, 2012

25）Yamashita D, et al：Neuroprotective effects of cutamesine, a ligand of the sigma-1 receptor chaperone, against noise-induced hearing loss. J Neurosci Res 93：788-795, 2015

26）Hoya N, et al：A novel animal model of acute cochlear mitochondrial dysfunction. Neuroreport 15：1597-1600, 2004

27）Okamoto Y, et al：Permanent threshold shift caused by acute cochlear mitochondrial dysfunction is primarily mediated by degeneration of the lateral wall of the cochlea. Audiol Neurootol 10：220-233, 2005

28）Kamiya K：Mesenchymal stem cell transplantation accelerates hearing recovery through the repair of injured cochlear fibrocytes. Am J Pathol 171：214-226, 2007

29）Mizutari K, et al：Caspase inhibitor facilitates recovery of hearing by protecting the cochlear lateral wall from acute cochlear mitochondrial dysfunction. J Neurosci Res 86：215-222, 2008