The long term objective of the proposed research is to elucidate the functions and regulation of the tissues of the blood-brain barrier (microvasculature) and blood-CSF barrier (choroid plexus). There are three specific objectives for the current research: 1) To determine whether brain-barrier tissues may serve as end organs for atriopeptins (AP's), recently identified salt and water regulatory factors secreted from the heart; 2) To determine whether the choroid plexus has an immunological function for the brain; 3) To determine and characterize the beta-adrenergic regulation of neutral amino acid uptake into cerebral microvessels. Preliminary data from this laboratory support the existence of all three of the above functions. The research will utilize a combination of biochemical and physiological methods, including receptor regulation of cyclic nucleotides, cell separation and isolation techniques, determinations of hormone effects on CSF production via ventricular-cisternal perfusion, measurements of antigen-specific cytotoxicity and lymphocyte activation by barrier tissues, and measurements of isotope uptake and efflux in isolated barrier tissue cells. The three specific objectives have clinical implications for: 1) control of cerebral edema and hydrocephalus; 2) initiation of immunological responses to CNS bacterial and viral infections, and surveillance of tumor cells in CSF; and 3) brain nutrition and delivery of drugs for treatment of certain CNS diseases (e.g., Parkinsonism).
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