Brain edema 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 in the extracellular space of the brain. The goals of this research project are to understand more definitely the mechanisms by which this cell achieves net movement of water and solute and the relationship between this cell function and the pathogenesis of cytotoxic edema. Cell volume and metabolic responses of astrocytes to conditions of altered osmolarity will be correlated with movements of ions and putative """"""""idiogenic"""""""" amino acid osmolytes. The contributions of various ion channels and transport systems to these volume responses will be defined. The control of intracellular calcium of ion movements induced by antiosmotic exposure will be explored. Finally, the effects of astrocyte volume regulation and solute transport of factors which may contribute to cytotoxic edema in Reye's syndrome, hepatic encephalopathy, and conditions of reduced brain energy metabolic state such as ischemia will be studied. In in vivo studies, the ability of the brain to maintain water homeostasis will be quantified. Blood-brain barrier integrity will be determined and solute movements which contribute to water homeostasis in normal rats and rats subjected to states of cerebral edema will be compared with in vitro studies of astrocytes. These studies will provide a greater understanding of the mechanisms of astrocyte volume regulation under physiologic conditions and the processes responsible for the genesis and resolution of brain edema in pathologic states. Knowledge of these mechanisms will provide new testable hypotheses relating to the development and resolution of brain edema in critical clinical states including Reye's syndrome, hepatic encephalopathy, and ischemia. These studies also 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 #
2R01NS023218-05A1
Application #
3406445
Study Section
Neurology A Study Section (NEUA)
Project Start
1986-09-01
Project End
1994-03-31
Budget Start
1991-04-01
Budget End
1992-03-31
Support Year
5
Fiscal Year
1991
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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