Blast Wave Effects: Hearing, Memory, Therapy

描述（由申请人提供）：爆炸波爆炸是军事人员听力损失的主要原因，但爆炸也会引起创伤性脑损伤和记忆力受损。在初步实验中，我们已经证明，暴露于冲击波和连续噪音不仅会损害内耳，还会导致海马体细胞死亡，抑制神经发生并损害记忆功能。本研究的目的是：（1）评估冲击波与连续噪声暴露导致的功能性听力损伤和耳蜗损伤（坏死和凋亡）的程度。(2)确定D-甲硫氨酸（一种抗氧化剂和凋亡剂）对冲击波引起的听力损伤和耳蜗病变的保护程度。(3)确定冲击波暴露破坏记忆功能、诱导细胞死亡和抑制海马神经发生的程度。(4)确定D-甲硫氨酸是否可以防止冲击波引起的记忆障碍，防止海马细胞死亡和恢复海马神经发生。这些研究将提供新的机制的见解，在冲击波和噪声引起的内耳和海马损伤的坏死和凋亡的作用，以及抗氧化剂，抗凋亡药物治疗是否可以预防或改善冲击波对内耳和海马的损伤。

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.