Using quantitative autoradiography, we will characterize altered regional brain physiology and metabolism in a murine model of focal herpes simplex virus (HSV) encephalitis. Using radiolabeled metabolic tracers injected in vivo and computerized image analysis of brain section autoradiograms, we will examine regional uptake of antiviral pyrimidine nucleosides (14C-FMAU, 14C-FIAC and 125I-FIAC), glucose utilization (14C-2-deoxyglucose), blood-brain barrier permeability (14C-alpha-aminoisobutyric acid and 14C-sucrose), tissue pH (14C-DMO), and antiviral antibody sequestration (125I-labeled monoclonal antibody). Contributions of both viral infection and secondary host immune and inflammatory responses to the metabolic derangements will be assessed within infected regions as well as in uninfected brain structures. These results will provide unique information bearing on the pathogenesis of neurologic dysfunction accompanying HSV encephalitis and hopefully also lead to new, more effective diagnositc and therapeutic strategies in man.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS019048-03
Application #
3399048
Study Section
Neurology A Study Section (NEUA)
Project Start
1983-01-01
Project End
1985-12-31
Budget Start
1985-01-01
Budget End
1985-12-31
Support Year
3
Fiscal Year
1985
Total Cost
Indirect Cost
Name
Sloan-Kettering Institute for Cancer Research
Department
Type
DUNS #
064931884
City
New York
State
NY
Country
United States
Zip Code
10065
Price, R W; Brew, B; Sidtis, J et al. (1988) The brain in AIDS: central nervous system HIV-1 infection and AIDS dementia complex. Science 239:586-92
Brew, B J; Sidtis, J J; Rosenblum, M et al. (1988) AIDS dementia complex. J R Coll Physicians Lond 22:140-4
Price, R W; Sidtis, J; Rosenblum, M (1988) The AIDS dementia complex: some current questions. Ann Neurol 23 Suppl:S27-33
Brew, B J; Rosenblum, M; Price, R W (1988) Pathogenetic implications of neuropathological findings in the AIDS dementia complex. Psychopharmacol Bull 24:307-10
Michaels, J; Price, R W; Rosenblum, M K (1988) Microglia in the giant cell encephalitis of acquired immune deficiency syndrome: proliferation, infection and fusion. Acta Neuropathol 76:373-9