CEREBRAL BLOOD FLOW AND METABOLISM IN MENINGITIS

本研究建议的目的是研究 细菌性脑膜炎的病理生理和代谢后果 在兔子模型中。 研究的主要领域是 脑血流与脑血管自动调节、改变 包括葡萄糖利用在内的大脑代谢过程 和乳酸的产生，以及与发育有关的因素 颅内压增高 这些异常表现在 患有细菌性脑膜炎的儿童和成人， 导致神经系统后遗症，这是常见的。 我们将尝试定义这些之间的相互关系 变量和致病因素。 的作用 微生物因素和宿主炎症反应的影响 评估其对联合国的独立贡献， 伴随脑膜炎的神经紊乱。 将开展研究 在这个实验室里，一个建立良好的脑膜炎模型， 我们可以用它同时进行重复测量 一系列生理和生化参数。 我们将连续测定脑血流量， 脑氧糖代谢率、脑乳酸 产酸、颅内压和脑脊液 白色血细胞计数、细菌滴度和 葡萄糖和乳酸盐。 选择性颅内操作 压力，乳酸，细菌滴度和浓度 细菌细胞壁成分和白色血细胞反应将 使我们能够评估它们对改变的相对贡献 脑灌注 拟议的研究将定义病理生理学的演变， 细菌性脑膜炎的生物化学变化和病原学 造成这些变化的因素，并建立 循环和代谢改变之间的相互关系。

The objectives of this research proposal are to examine the pathophysiologic and metabolic consequences of bacterial meningitis in a rabbit model. Principal areas of study are changes in cerebral blood flow and cerebrovascular autoregulation, alteration in metabolic processes in the brain including glucose utilization and lactic acid production, and the factors relating to development of intracranial hypertension. These abnormalities are seen in children and adults with bacterial meningitis and are likely to contribute to neurologic sequelae which commonly occur. We will attempt to define the interrelationships between these variables and the etiologic factors responsible for them. The role of microbiologic factors and the host inflammatory response will be valuated to assess their independent contribution to the derangements which accompany meningitis. Studies will be developed in this laboratory, of a well established model of meningitis the rabbit with which we can make simultaneous and repeated measurement of a number of physiologic and biochemical parameters. We will perform sequential determinations of cerebral blood flow, cerebral metabolic rate for oxygen and glucose, cerebral lactic acid production, intracranial pressure, and cerebrospinal fluid white blood cell counts, bacterial titers and concentration of glucose and lactate. Selective manipulation of intracranial pressure, lactic acid, bacterial titers and concentration of bacterial cell wall components, and white blood cell response will allow us to assess their relative contribution to alterations in cerebral perfusion. The proposed studies will define the evolution of pathophysiologic and biochemical changes in bacterial meningitis and the etiologic factors responsible for these changes, and establish the interrelationships between circulatory and metabolic alterations.