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.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Clinical Investigator Award (CIA) (K08)
Project #
5K08NS001235-03
Application #
3084056
Study Section
Neurological Disorders Program Project Review A Committee (NSPA)
Project Start
1988-04-01
Project End
1993-03-31
Budget Start
1990-04-01
Budget End
1991-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
Nationwide Children's Hospital
Department
Type
DUNS #
City
Columbus
State
OH
Country
United States
Zip Code
43205
Lo, W D; Wolny, A; Boesel, C (1994) Blood-brain barrier permeability in staphylococcal cerebritis and early brain abscess. J Neurosurg 80:897-905
Lo, W D; Wolny, A C; Timan, C et al. (1993) Blood-brain barrier permeability and the brain extracellular space in acute cerebral inflammation. J Neurol Sci 118:188-93
Lo, W D; McNeely, D L; Boesel, C W (1991) Blood-brain barrier permeability in an experimental model of bacterial cerebritis. Neurosurgery 29:888-92
Lo, W D; Barohn, R J; Bobulski, R J et al. (1990) Centronuclear myopathy and type-1 hypotrophy without central nuclei. Distinct nosologic entities? Arch Neurol 47:273-6
Lo, W D; Sloan, H R; Fahey, B P et al. (1990) Tangier disease in a black patient: an unusual clinical presentation. Am J Med 89:105-8
Applegate, M S; Lo, W (1989) Febrile seizures: current concepts concerning prognosis and clinical management. J Fam Pract 29:422-8