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.
