Fig. 20.1
Summary of critical events and therapeutic drugs after hair cell damage in the apoptotic process. Just after hair cell damage, ROS and JNK are activated. Several hours later, cytochrome c and caspase are activated. At each step, inhibitors such as anti-ROS, anti-JNK, or anti-caspase are effective against hair cell damages
.
20.5 Other Therapeutic Drugs
20.5.1 Neurotrophic Factors
Neurotrophic factors are important for development, differentiation, or survival of neurons. In non-neuronal tissues such as inner ear, some neurotrophic factors are important for normal development and have a protective effect against hair cell damage. Brain-derived neurotrophic factor (BDNF) was effective for inner ear against drug-induced damage in vivo [54], and neurotrophin-3 (NT-3) is also important for developing auditory sensory epithelium. Both BDNF and NT-3 were found to be effective against ototoxic drug in rat auditory hair cells [55]. Although these neurotrophic protections of hair cells against drug and noise trauma appear to be statistically significant, the extent of protection is less than enough for clinical use in future.
20.5.2 Growth Factors
The insulin-like growth factor (IGF) signaling is very important in the inner ear development [56]. IGF-1 is effective against hair cell damage by noise trauma in vivo and by ototoxic drugs in vitro [57, 58]. IGF-1 maintained the hair cells in injured cochlea through the activation of both the PI3K/Akt and MEK/ERK pathways [59]. And the involvement of epidermal growth factor (EGF) and (TGF-α) in the inner ear is suggested. TGF-α and EGF (plus insulin) were reported to stimulate cell proliferation in mammalian vestibular sensory epithelium [60].
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