Inflammation after traumatic brain injury

描述：（逐字摘自申请人摘要）创伤性脑损伤（TBI） 引发一连串的炎症过程， 最初的伤害。最近的实验数据表明，创伤后 温度控制显著影响炎症反应， 包括多形核白细胞（PMNL）的积累和诱导 一氧化氮合酶活性。拟议的研究将建立在这些基础上 以前的结果，并研究细胞，生物化学和分子 温度敏感性炎症事件的潜在机制， 创伤性脑损伤针对具体问题提出了三个具体目标 关于这个调查问题。在第一个具体目标中，实验将 重点关注创伤后炎症的诱发因素， 细胞因子这些调查将确定伤害的重要性 严重程度对TBI的细胞因子反应，以及确定第一个 时间的影响，创伤后温度操纵这些 炎症诱导物。在第二个目标中，我们将研究主要的 这些炎症分子对压力信号的作用，包括p38 丝裂原活化蛋白激酶、转录因子NF-κ B以及 内皮细胞粘附分子ICAM-1、P-选择素的表达。这些 研究被认为是重要的，因为它们将确定是否 创伤后低体温与影响 的促炎细胞因子，有一个主要影响二级信号 途径。在最后的目标，我们将确定的差异影响， 低温对炎症级联反应的选择性方面的影响。为此， 转基因和基因敲除小鼠将在常温下进行研究， 低温条件下。这些研究将针对所调查的损伤过程 目标一和目标二，评估急性和慢性结构性和 低温保护中特定损伤过程的功能后果。 建立了ELISA定量方法，组织病理学分析， 原位杂交，分子技术，以及大量的 大鼠和小鼠的行为任务，将用于补充整体 提议这种创伤研究的新方法应该提供重要的数据 关于炎症过程和温度之间的相互作用。

DESCRIPTION: (Verbatim from applicant's abstract) Traumatic brain injury (TBI) initiates a cascade of inflammatory processes that can serve to exacerbate the initial injury. Recent experimental data indicate that post-traumatic temperature manipulations significantly influence the inflammatory responses, including the accumulation of polymorphonuclear leukocytes (PMNL) and inducible nitric oxide synthase activity. The proposed studies will build on these previous results and investigate the cellular, biochemical, and molecular mechanisms underlying the temperature-sensitive inflammatory events seen after TBI. Three specific aims are proposed that focus on specific questions regarding this investigative issue. In the first specific aim, experiments will focus on inducers of post-traumatic inflammation, with emphasis on inflammatory cytokines. These investigations will determine the importance of injury severity on the cytokine response to TBI as well as determining for the first time the effects of post-traumatic temperature manipulations of these inflammatory inducers. In the second aim, we will investigate the primary actions of these inflammatory molecules on stress signals, including p38 mitogen-activated protein kinase, the transcriptional factor, NF-kB, as well as the expression of endothelial adhesion molecules (ICAM-1, P-selectin). These studies are felt to be important because they will determine whether post-traumatic hypothermia in contrast to affecting the production and release of the pro-inflammatory cytokines, have a primary effect on secondary signaling pathways. In the final aim, we will determine the differential effects of hypothermia on selective aspects of the inflammatory cascade. For this aim, transgenic and knockout mice will be investigated under normothermic and hypothermic conditions. These studies will target injury processes investigated in Aims I and II and assess both the acute and more chronic structural and functional consequences of specific injury processes in hypothermia protection. Established quantitative methods of ELISA's, histophatological analysis, in situ hybridization, molecular techniques, as well as a large battery of behavioral tasks in rats and mice, will be used to complement the overall proposal. This new approach to trauma research should provide important data concerning interactions between inflammatory processes and temperature.