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Recent Patents on CNS Drug Discovery (Discontinued)

Eiditor-in-Chief

ISSN (Print): 1574-8898
ISSN (Online): 2212-3954

The Injured Cochlea as a Target for Inflammatory Processes, Initiation of Cell Death Pathways and Application of Related Otoprotective Strategies

Author(s): Ralph N. Abi-Hachem, Azel Zine and Thomas R. Van De Water

Volume 5 , Issue 2 , 2010

Page: [147 - 163] Pages: 17

DOI: 10.2174/157488910791213121

Price: $58

Abstract

One of the causes of sensorineural hearing loss is the loss of auditory hair cells following exposure to environmental stresses. Auditory hair cell death in response to cochlear trauma occurs via both necrosis and apoptosis. Apoptosis of hair cells involves the caspase and MAPK/JNK pathways which are activated by oxidative stress and secretion of inflammatory cytokines in response to trauma. Identification of the pathways that lead to apoptosis provides therapeutic targets for the conservation of hearing. Antioxidants reduce the level of reactive oxygen species and reactive nitrogen species generated by oxidative stress in response to acoustic trauma, aminoglycoside and platinum-based drugs. Caspase inhibitors affect both the extrinsic and intrinsic apoptotic pathways, thereby reducing cisplatin, aminoglycoside, hydraulic trauma and ischemia-induced hearing losses. Corticosteroid therapy reduces inflammation and inhibits apoptosis while activating pro-survival pathways in the organ of Corti following exposure to noise, vibration, cisplatin, aminoglycoside, ischemia/reperfusion injury, bacterial meningitis and electrode insertion trauma. Inhibitors of JNK signaling pathway prevent apoptosis of auditory hair cells following electrode insertion trauma, acute labyrinthitis, acoustic trauma and aminoglycoside ototoxicity. This review provides an overview of the different pathways involved in auditory hair cell death following an environmental stress and both traditional and newly developed drugs that are currently being studied or used for the treatment of acute hearing loss. Recent patents related to otoprotective strategies to conserve hearing and auditory hair cells are also discussed in this review.

Keywords: Trauma, inflammation, ototoxicity, cochlea, sensorineural hearing loss, apoptosis, auditory hair cells, otoprotection, antioxidants, corticosteroids, cochlear implantation, caspase, c-Jun N-terminal kinase


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