Our work has established the existence of a system of supraependymal cells of hypothalamic 3rd ventricle with morphological, phagocytic and histochemical features of cells in the monocyte/macrophage line. We have also shown the cells to have surface receptors for the Fc fragment of lgG antibody, an important functional feature of macrophages. We have studied supraependymal cells in situ, using scanning and transmission electron microscopy (SEM and TEM) and have grown them in tissue culture in order to characterize them immunologically. Our hypotheses are (1) that under normal conditions supraependymal macrophages clear the CSF and ventricular surfaces of debris resulting from intraventricular and ependymal cells growth and death and from other metabolic activities; and (2) that together ependymal cells and supraependymal macrophages function as a first line of defense against viral and bacterial invasion of the brain. The work in this proposal is designed to serve our objective of (1) the detailed characterization of the structure, functions, kinetics and origins of macrophages of the brain ventricles under normal and pathological conditions, and the developmental changes these features undergo with time, from birth into old age; and (2) an understanding of dynamic morphological changes of the 3rd ventricle during developmental and cyclical events within the hypothalamus. Specifically, using immunological techniques, we will examine supraependymal cells from mice and hamsters for typical macrophage surface receptors and antigens and test their responses to chemotactic agents and to bacteria. We will follow the development from birth to old age of these features and of the cells' histochemical and phagocytic characteristics. With SEM and TEM we will study the developmental and metabolic changes in morphology of supraependymal macrophages and their relationship to changes in ependyma and intraventricular structures such as growth cones and neurons. Characterization of the functional and developmental capabilities of a ventricular system of macrophages is important in view of the peculiar vulnerability of the brain to immediate or delayed damage by conventional and unconventional viruses and also the age-related susceptibility of the brain to perinatal infections with certain known viruses and possibly to other ostensibly banal, inapparent or latent viral infections.
NIH ExPorter
NIH ExPorter