The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies.

The injured cochlea as a target for inflammatory processes, initiation of cell death pathways and application of related otoprotectives strategies. Recent Pat CNS Drug Discov. 2010 Jun;5(2):147-63 Authors: Abi-Hachem RN, Zine A, Van De Water TR 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 apopt...
Source: Recent Patents on CNS Drug Discovery - Category: Drugs & Pharmacology Tags: Recent Pat CNS Drug Discov Source Type: research