Hypoxia and hyperoxia decrease dehydrogenase (LDH) and protein content, cause cell edema, and disrupt cell membranes of primary cultures of astrocytes. Fructose-1, 6-diphosphate (FDP) + glucose (GLc) prevents these changes, but FDP or Glc alone does not. During hypoxia, Na+-K+ ATP-ase activity increases when FDP + Glc is present; it decreases with Glc or FDP alone. We postulate that the protective effects of FDP are either due to increased metabolism and maintenance of normal cellular ion homeostasis or to effects on oxygen free radical production and cell membrane destruction. To test our hypotheses, we will determine whether FDP increases metabolism and ATP content of hypoxic and hyperoxic astrocytes and neurons, whether FDP maintains normal intracellular concentrations of ions, whether FDP prevents cell edema, and whether FDP maintains membrane integrity and function. To determine whether FDP prevents the effects of oxygen free radicals on normoxic and hyperoxic cells, we will determine whether oxygen free radical production increases, whether membrane is altered. Membrane fatty acid composition will also be determined. These studies will provide new information about the effects of hypoxia and hyperoxia on astrocytes and neurons and about the mechanism by which FDP prevents detrimental effects of low and high oxygen. This information will increase our understanding of how cells are injured by abnormal oxygen states and may lead to new methods of brain protection.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS026092-03
Application #
3411725
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1988-04-01
Project End
1992-03-31
Budget Start
1990-04-01
Budget End
1992-03-31
Support Year
3
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of California San Francisco
Department
Type
Schools of Medicine
DUNS #
073133571
City
San Francisco
State
CA
Country
United States
Zip Code
94143
Kuluz, J W; Gregory, G A; Han, Y et al. (1993) Fructose-1,6-bisphosphate reduces infarct volume after reversible middle cerebral artery occlusion in rats. Stroke 24:1576-83
Yu, A C; Gregory, G A; Chan, P H (1989) Hypoxia-induced dysfunctions and injury of astrocytes in primary cell cultures. J Cereb Blood Flow Metab 9:20-8
Gregory, G A; Yu, A C; Chan, P H (1989) Fructose-1,6-bisphosphate protects astrocytes from hypoxic damage. J Cereb Blood Flow Metab 9:29-34