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VASCULAR PERMEABILITY AND BRAIN EDEMA IN BRAIN ABSCESS

脑脓肿中的血管通透性和脑水肿

基本信息

批准号：
3084058
负责人：
WARREN D LO
金额：
$ 7.78万
依托单位：
CHILDREN'S HOSPITAL (COLUMBUS)
依托单位国家：
美国
项目类别：
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/3084058
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

项目摘要

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.

脑部疾病中浮肿的出现被认为是由于血脑屏障功能受损，允许血管内物质扩散到脑实质。脑水肿是一种严重并发症，如脓肿、脑膜炎和肿瘤，但产生水肿的机制尚不清楚。这个该项目的长期目标是将这些机制定义为可以设计出改进的浮肿治疗方法。这个项目将研究感染时产生浮肿的机制大脑的一部分。该项目将采用一种老鼠模型葡萄球菌性脑脓肿检验细菌假说产品增加血脑屏障的通透性，以及促进感染区域的浮肿形成。这个具体目标是确定：1.当血脑屏障对血管内的渗透性物质相比，当白细胞迁移到脓肿部位；2.脑细胞外时间进程与血脑相比，空间的大小增加了屏障变得异常渗透性；3.无论是毒素还是金黄色葡萄球菌的亚细胞成分可影响血脑屏障通透性和细胞外间隙与整个细菌的程度相同。的渗透性将对整个动物进行血脑屏障的检查测量血管内示踪剂进入大脑的运动。白细胞的迁移将通过测量 ~(51)Cr标记的大鼠中性粒细胞进入脑内的运动。这个细胞外空间的大小将用离子- 一种选择性微电极，它将测量一种离子导入电极中的四烷基铵离子。这个毒素和葡萄球菌产品的影响将通过确定细菌的成分是否产生类似的血脑屏障通透性和血管大小的变化与活的葡萄球菌相比，胞外空间。