Brain swelling is a critical factor contributing to the mortality and morbidity of individuals with a wide variety of pathologic conditions. The astrocyte is thought to be important in maintaining water volume and electrolyte concentrations and the extracellular space of the brain. The goals of this research proposal include establishing more definitely this critical role of the astrocyte and investigating mechanisms by which this cell achieves net movement of water and solute. A third goal is to determine the relationship between this cell function and the pathogenesis of cytotoxic edema. Cell volume responses of primary cultured astrocytes to altered osmolarity will be studied as a model of astrocyte control of brain water. Techniques developed previously in this laboratory will be refined to permit quantitative measures of water and ion movements during hyper- and hypo-osmotic exposure. The contributions of various ion channels and transport systems to these volume responses will be identified. Finally, we shall study the effects on astrocyte volume regulation of factors which may contribute to the pathogenesis of cytotoxic edema in Reye's Syndrome and cerebral ischemia. We shall correlate these in vitro studies with in vivo states of cerebral edema by quantifying water and ion movements in the brains of animals exposed to those agents which affect astrocyte volume control in vitro. These studies will provide insight into the mechanisms of astrocyte volume control under physiological conditions and the processes important in the genesis and resolution of brain edema in pathologic conditions. Knowledge of these mechanisms will provide testable hypotheses relating to the production and resolution of brain edema in critical clinical states including Reye's Syndrome and cerebral ischemia. In addition, these studies may suggest rational therapies for cytotoxic brain edema.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS023218-04
Application #
3406449
Study Section
Neurological Sciences Subcommittee 1 (NLS)
Project Start
1986-09-01
Project End
1990-06-30
Budget Start
1989-04-01
Budget End
1990-06-30
Support Year
4
Fiscal Year
1989
Total Cost
Indirect Cost
Name
Wright State University
Department
Type
Schools of Medicine
DUNS #
City
Dayton
State
OH
Country
United States
Zip Code
45435
Olson, J E (1999) Osmolyte contents of cultured astrocytes grown in hypoosmotic medium. Biochim Biophys Acta 1453:175-9
Beetsch, J W; Olson, J E (1998) Taurine synthesis and cysteine metabolism in cultured rat astrocytes: effects of hyperosmotic exposure. Am J Physiol 274:C866-74
Olson, J E; Banks, M; Dimlich, R V et al. (1997) Blood-brain barrier water permeability and brain osmolyte content during edema development. Acad Emerg Med 4:662-73
Beetsch, J W; Olson, J E (1996) Hyperosmotic exposure alters total taurine quantity and cellular transport in rat astrocyte cultures. Biochim Biophys Acta 1290:141-8
Hilgier, W; Olson, J E; Albrecht, J (1996) Relation of taurine transport and brain edema in rats with simple hyperammonemia or liver failure. J Neurosci Res 45:69-74
Olson, J E; Kimelberg, H K (1995) Hypoosmotic volume regulation and osmolyte transport in astrocytes is blocked by an anion transport inhibitor, L-644,711. Brain Res 682:197-202
Olson, J E; Alexander, C; Feller, D A et al. (1995) Hypoosmotic volume regulation of astrocytes in elevated extracellular potassium. J Neurosci Res 40:333-42
Olson, J E; Evers, J A; Banks, M (1994) Brain osmolyte content and blood-brain barrier water permeability surface area product in osmotic edema. Acta Neurochir Suppl (Wien) 60:571-3
Hilgier, W; Olson, J E (1994) Brain ion and amino acid contents during edema development in hepatic encephalopathy. J Neurochem 62:197-204
Beetsch, J W; Olson, J E (1993) Taurine transport in rat astrocytes adapted to hyperosmotic conditions. Brain Res 613:10-5

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