Blast Wave Effects: Hearing, Memory, Therapy

描述(申请人提供)：冲击波爆炸是军事人员听力丧失的主要原因，但爆炸也会导致创伤性脑损伤和记忆力受损。在初步实验中，我们已经证明，暴露在冲击波和持续噪音中不仅会损害内耳，还会导致海马区细胞死亡，抑制神经发生，并损害记忆功能。该项目的目标是：(1)评估冲击波与持续噪声暴露所导致的功能性听力损害和耳蜗损伤(坏死和凋亡)的量。(2)测定抗氧化剂和细胞凋亡剂D-蛋氨酸对冲击波致听损伤和耳蜗病的保护作用。(3)确定冲击波暴露在多大程度上扰乱记忆功能、诱导细胞死亡和抑制海马区神经发生。(4)探讨D-蛋氨酸对冲击波所致记忆损伤的保护作用、对海马细胞死亡的保护作用及对海马神经再生的恢复作用。这些研究将对冲击波和噪声引起的内耳和海马区损伤中的坏死和细胞凋亡的作用，以及抗氧化剂、抗凋亡药物治疗是否能预防或改善冲击波对内耳和海马区的损伤提供新的机制见解。

DESCRIPTION (provided by applicant): Blast wave explosions are a major cause of hearing loss among military personnel, but blasts can also induce traumatic brain injury and impair memory. In preliminary experiments, we have shown that exposure to blast waves and continuous noise not only damaged the inner ear, but caused cell death in the hippocampus, suppressed neurogenesis and impaired memory function. The goals of this project are to: (1) Assess the amount of functional hearing impairment and cochlear damage (necrosis and apoptosis) that results from blast wave vs. continuous noise exposures. (2) Determine the extent to which D-methionine, an anti-antioxidant and apoptotic agent, can protect against blast wave induced hearing impairment and cochlear pathology. (3) Determine the extent to which blast wave exposure disrupts memory function and induces cell death and suppresses neurogenesis in the hippocampus. (4) Determine if D-methionine can protect against blast wave induced memory impairments, prevent hippocampal cell death and restore hippocampal neurogenesis. These studies will provide new mechanistic insights on the role of necrosis and apoptosis in blast and noise induced injury to the inner ear and hippocampus and whether antioxidant, anti-apoptotic drug therapy can prevent or ameliorate blast wave injury to the inner ear and hippocampus.