Figure 4.

Cell death signaling following acoustic trauma. Acoustic trauma can promote edema of the stria vascularis, resulting in cochlear hypoxia, formation of ROS, and oxidative stress. Noise trauma can also stimulate the spiral ligament to express cytokines (such as TNFα and IL-1β) and chemokines that initiate migration of leukocytes to the cochlea; leukocytes will then release a number of other pro-inflammatory factors and free radicals that propagate the inflammatory process. Oxidative stress and pro-inflammatory cytokines can travel to the inner hair cells (IHC) and outer hair cells (OHCs) of the organ of Corti and induce intrinsic and extrinsic apoptotic signaling cascades. Prolonged activation of JNK and induction of RIPK1/3 activity can promote necrotic cell death. Glucocorticoids have demonstrated protection against acoustic trauma, in part by reducing leukocyte migration, decreasing expression of pro-inflammatory factors, and activating NFκB inhibition of JNK signaling. Antioxidants and free radical scavengers can neutralize ROS and downstream effects of oxidative stress. Inhibitors of JNK can also mitigate noise-induced loss of auditory HCs by preventing downstream signaling cascades that lead to apoptosis and necrosis.