The role of gender on post-traumatic inflammation

性别对创伤后炎症的作用

• 批准号: 6819713
• 负责人: Helen M Bramlett
• 金额: $ 21.59万
• 依托单位: UNIVERSITY OF MIAMI SCHOOL OF MEDICINE
• 依托单位国家: 美国
• 财政年份: 2002
• 资助国家: 美国
• 起止时间: 2002-12-01 至 2006-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6819713
• 关键词: role; gender; post; traumatic; inflammation

EXCEED THE SPACE PROVIDED. The efficacy of estrogen treatment in several injury models has been previously reported. Our own recent work has demonstrated a reduction in contusion volumes following traumatic brain injury (TBI) in female rats versus males or ovariectomized females. Although several mechanistic pathways for this neuroprotection have been explored, one that has not and is important after TBI is inflammation. TBI produces a robust inflammatory response that is both acute and chronic in duration. Several investigators using other models have reported the ability of estrogen to inhibit specific components of the inflammatory cascade. The proposed studies will assess differences between males and females after TBI with regard to post-traumatic inflammation. Four specific aims are proposed to address this issue. In specific aim 1, we will measure levels of proinflammatory cytokines and determine the cellular source of these initiators of inflammation. These studies will provide novel data on differences between males and females and in addition, by using ovariectomized females, the influence of reproductive steroids. In the second aim, we will study regional patterns of iNOS expression and determine if this response is sex and hormone-dependent. Because iNOS has been implicated in the pathogenesis of TBI, this inflammatory response to trauma requires investigation in the present setting. Specific aim 3 will assess whether estrogen's effect on the inflammatory cascade after TBI is due to antioxidant properties or receptor-mediated mechanisms. Because estrogen has been reported to effect various components of the inflammatory cascade, its effect on trauma-induced inflammatory processes requires further investigation. Results from this study will provide novel data for the potential use of neurohormones in the treatment of TBI. In the final aim, estrogen isomers or specific estrogen receptor antagonist/agonist will be administered after TBI to assess recovery of function. Taken together, these experiments will provide new data on the importance of neurohormones on structural and functional outcome after TBI. Established methods including rodent models of TBI, behavioral tests, as well as immunocytochemical and molecular approaches will be used in this proposal. PERFORMANCE SITE ========================================Section End===========================================

超出所提供的空间。先前已报道过雌激素治疗在几种损伤模型中的功效。我们最近的工作表明，与雄性或切除卵巢的雌性大鼠相比，雌性大鼠在创伤性脑损伤（TBI）后挫伤体积有所减少。尽管已经探索了这种神经保护的几种机制途径，但在 TBI 后尚未探索但很重要的是炎症。 TBI 会产生强烈的炎症反应，其持续时间既有急性的，也有慢性的。一些使用其他模型的研究人员报告了雌激素抑制炎症级联的特定成分的能力。拟议的研究将评估 TBI 后男性和女性之间在创伤后炎症方面的差异。提出了四个具体目标来解决这个问题。在具体目标 1 中，我们将测量促炎细胞因子的水平并确定这些炎症引发剂的细胞来源。这些研究将提供有关男性和女性之间差异的新数据，此外，通过使用卵巢切除的女性，研究生殖类固醇的影响。第二个目标是，我们将研究 iNOS 表达的区域模式，并确定这种反应是否依赖于性别和激素。由于 iNOS 与 TBI 的发病机制有关，因此目前需要对这种对创伤的炎症反应进行研究。具体目标 3 将评估雌激素对 TBI 后炎症级联的影响是否归因于抗氧化特性或受体介导的机制。由于据报道雌激素会影响炎症级联的各个组成部分，因此其对创伤诱发的炎症过程的影响需要进一步研究。这项研究的结果将为神经激素在 TBI 治疗中的潜在用途提供新的数据。最终目标是在 TBI 后给予雌激素异构体或特定雌激素受体拮抗剂/激动剂来评估功能恢复情况。总而言之，这些实验将提供关于神经激素对 TBI 后结构和功能结果重要性的新数据。本提案将使用已建立的方法，包括 TBI 啮齿动物模型、行为测试以及免疫细胞化学和分子方法。表演网站==========================================部分结束====== =======================================