Blast Wave Effects: Hearing, Memory, Therapy

描述（由申请人提供）：冲击波爆炸是军事人员听力损失的主要原因，但爆炸也会导致创伤性脑损伤和记忆力减退。在初步实验中，我们已经证明，暴露在爆炸波和持续噪音中不仅会损伤内耳，还会导致海马细胞死亡，抑制神经发生，损害记忆功能。本项目的目标是：(1)评估爆炸波与持续噪声暴露导致的功能性听力损伤和耳蜗损伤（坏死和细胞凋亡）的数量。(2)确定d -蛋氨酸作为抗氧化和细胞凋亡的药物，在多大程度上对冲击波性听力损伤和耳蜗病理有保护作用。(3)确定爆炸波暴露在多大程度上破坏记忆功能、诱导细胞死亡和抑制海马神经发生。(4)确定d -蛋氨酸是否可以预防冲击波引起的记忆损伤，防止海马细胞死亡，恢复海马神经发生。这些研究将为爆炸和噪声引起的内耳和海马损伤中坏死和凋亡的作用以及抗氧化、抗凋亡药物治疗是否可以预防或改善爆炸波对内耳和海马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.