Astrocytic processes form the surface of the mammalian brain and entirely surround all blood vessels in the brain. One approach to understanding the function of these astrocytic processes is to examine the biochemical characteristics and function of a specific membrane-associated protein which is highly concentrated in their membranes. This protein, which has been termed """"""""assemblies"""""""" from its appearance in freeze-fractured tissue, is of further interest in that it undergoes a unique conformational change within seconds of circulatory arrest. It is possible that this conformational change alters astrocytic membrane permeability, causing the astrocytic swelling which complicates ischemic brain injury. Tissues culture methods have been devised which elicit the differentiation of assemblies in primary astrocytes, and serum factors which influence astrocyte lineage and differentiation are under study. Cultures are being used to examine more precisely the etiology of the conformational change that follows circulatory arreest. In preliminary experiments, a band in electrophoretic gels has been identified which is correlated with the presence of assemblies, and which will be used as one approach to the generation of monoclonal antibodies. Such antibodies will serve to facilitate biochemical characteization of the assembly protein, and can be used to develop a quantitative assay for it that will greatly simplify studies of astrocyte development and lineage. Monoclonal and polyclonal antibodies may also serve as probes for the function of the protein. As we learn about this property of astrocytes, we may be able to design better responses to the clinical problems of astrocytic swelling in ischemic and traumatic injury.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
1R01NS022614-01A1
Application #
3405245
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-08-01
Project End
1989-07-31
Budget Start
1986-08-01
Budget End
1987-07-31
Support Year
1
Fiscal Year
1986
Total Cost
Indirect Cost
Name
Case Western Reserve University
Department
Type
Schools of Medicine
DUNS #
077758407
City
Cleveland
State
OH
Country
United States
Zip Code
44106
Landis, D M (1994) The early reactions of non-neuronal cells to brain injury. Annu Rev Neurosci 17:133-51
Pozzo Miller, L D; Mahanty, N K; Connor, J A et al. (1994) Spontaneous pyramidal cell death in organotypic slice cultures from rat hippocampus is prevented by glutamate receptor antagonists. Neuroscience 63:471-87
Pozzo Miller, L D; Landis, D M (1993) Cytoplasmic structure in organotypic cultures of rat hippocampus prepared by rapid freezing and freeze-substitution fixation. Synapse 13:195-205
Landis, D M; Welter, E; Skordeles, C (1991) A novel epitope expressed on the surface of developing and mature astrocytes. Neuroscience 45:467-77
Landis, D M; Weinstein, L A; Skordeles, C J (1991) Effects of dexamethasone on the differentiation of membrane structure in cultured astrocytes. Glia 4:335-44
Landis, D M; Weinstein, L A; Skordeles, C J (1990) Serum influences the differentiation of membrane structure in cultured astrocytes. Glia 3:212-21
Landis, D M; Reese, T S (1989) Substructure in the assemblies of intramembrane particles in astrocytic membranes. J Neurocytol 18:819-31