VASCULAR PERMEABILITY AND BRAIN EDEMA IN BRAIN ABSCESS

脑脓肿中的血管通透性和脑水肿

• 批准号: 3084057
• 负责人: WARREN D LO
• 金额: $ 8.51万
• 依托单位: CHILDREN'S HOSPITAL (COLUMBUS)
• 依托单位国家: 美国
• 财政年份: 1988
• 资助国家: 美国
• 起止时间: 1988-04-01 至 1993-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/3084057
• 关键词: Staphylococcus aureus; Staphylococcus infection; bacterial toxins; blood brain barrier; brain edema; cell migration; disease /disorder model; laboratory rat; leukocyte activation /transformation; membrane permeability; microelectrodes; neutrophil

The presence of edema in brain disease is thought to be due to impaired blood-brain barrier function permitting intravascular substances to diffuse into the brain parenchyma. Brain edema is a serious complication of diseases such as abscess, meningitis, and tumors, but the mechanisms producing edema are unknown. The long-term goal of this project is to define those mechanisms so that improved treatment for edema can be designed. This project will examine the mechanism of edema production in an infection of the brain. The project will employ a rat model of a staphylococcal brain abscess to test the hypothesis that bacterial products increase the permeability of the blood-brain barrier, and promote the formation of edema in an infected region. The specific aims are to determine: 1. The time course when the blood-brain barrier becomes permeable to intravascular substances as compared to when leukocytes migrate into the abscess site; 2. The time course when the brain extracellular space increases in size as compared to when the blood-brain barrier becomes abnormally permeable; 3. Whether toxins or subcellular components of Staphylococcus aureus can affect blood-brain barrier permeability and the extracellular space to the same extent as the whole bacteria. The permeability of the blood-brain barrier will be examined in the whole animal by measuring the movement of an intravascular tracer into the brain. Leukocyte migration will be determined by measuring the movement of 51Cr labelled rat neutrophils into the brain. The size of the extracellular space will be measured with an ion- selective microelectrode which will measure the diffusion of a tetraalkylammonium ion from an ionophoresis electrode. The effect of toxins and staphylococcal products will be measured by determining if components of the bacteria produce similar changes in blood-brain barrier permeability and the size of the extracellular space when compared to live staphylococci.

脑水肿的存在被认为是由于 血脑屏障功能受损， 物质扩散到脑实质中。 脑水肿是一种 严重并发症的疾病，如脓肿，脑膜炎， 肿瘤，但产生水肿的机制是未知的。 的 该项目的长期目标是定义这些机制， 可以设计出更好的水肿治疗方法。 这个项目 将研究感染时水肿产生的机制 大脑。 该项目将采用一种大鼠模型， 葡萄球菌脑脓肿，以测试假设， 产品增加血脑屏障的渗透性， 促进感染部位水肿的形成。 的 具体目标是确定：1。时间进程，当 血脑屏障变得可渗透血管内 与白细胞迁移到 脓肿部位; 2.当大脑细胞外 与血脑相比， 屏障变得异常可渗透; 3. 无论是毒素还是 金黄色葡萄球菌的亚细胞成分可以影响 血脑屏障通透性和细胞外空间， 与整个细菌的程度相同。 的渗透性 通过以下方法检查整个动物的血脑屏障： 测量血管内示踪剂进入大脑的运动。 白细胞迁移将通过测量 51 Cr标记的大鼠中性粒细胞进入大脑。 的 细胞外间隙的大小将用离子测量， 选择性微电极，将测量扩散的 四烷基铵离子从离子电泳电极。 的 毒素和葡萄球菌产品的影响将通过以下方法进行测量： 确定细菌的成分是否产生类似的 血脑屏障通透性的变化和脑组织的大小 与活葡萄球菌相比，