This proposal seeks to study a clinically important disease, hyponatremia (low sodium in blood), which can result in brain damage. This application seeks to study the pathogenesis of hyponatremic encephalopathy via a multidisciplinary approach, with a goal of elucidating a mechanism by which failure of various adaptive mechanisms can induce hyponatremic encephalopathy. The applicant proposes to use proton magnetic resonance imaging (MRI) of the brain in vivo to explore possible structural changes and phosphorus (31-P) nuclear magnetic resonance spectroscopy (MRS) to evaluate cerebral metabolism in vivo. Pathologic alterations will be confirmed by histological techniques and correlated with MRI/MRS results. Additionally, Ca+ +, Na+, and K+ transport will be determined in vitro using synaptosomes prepared from the brain cerebral cortex. The effects of hormones with established and putative effects on cerebral fluid homeostasis will also be evaluated both in vivo and in vitro to ascertain whether specific neuroendocrine factors are responsible for the female predilection to hyponatremic encephalopathy.

Agency
National Institute of Health (NIH)
Institute
National Institute on Aging (NIA)
Type
Research Project (R01)
Project #
1R01AG008575-01A2
Application #
3120306
Study Section
Neurology A Study Section (NEUA)
Project Start
1991-06-01
Project End
1994-05-31
Budget Start
1991-06-01
Budget End
1992-05-31
Support Year
1
Fiscal Year
1991
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
Ayus, J C; Armstrong, D; Arieff, A I (2006) Hyponatremia with hypoxia: effects on brain adaptation, perfusion, and histology in rodents. Kidney Int 69:1319-25
Fraser, C L; Arieff, A I (2001) Na-K-ATPase activity decreases with aging in female rat brain synaptosomes. Am J Physiol Renal Physiol 281:F674-8
Arieff, A I; Kronlund, B A (1999) Fatal child abuse by forced water intoxication. Pediatrics 103:1292-5
Ayus, J C; Arieff, A I (1999) Chronic hyponatremic encephalopathy in postmenopausal women: association of therapies with morbidity and mortality. JAMA 281:2299-304
Arieff, A I (1999) Fatal postoperative pulmonary edema: pathogenesis and literature review. Chest 115:1371-7
Sarfaraz, D; Fraser, C L (1999) Effects of arginine vasopressin on cell volume regulation in brain astrocyte in culture. Am J Physiol 276:E596-601
Arieff, A I (1998) Postoperative hyponatraemic encephalopathy following elective surgery in children. Paediatr Anaesth 8:1-4
Fraser, C L; Arieff, A I (1997) Epidemiology, pathophysiology, and management of hyponatremic encephalopathy. Am J Med 102:67-77
Vexler, Z S; Roberts, T P; Bollen, A W et al. (1997) Transient cerebral ischemia. Association of apoptosis induction with hypoperfusion. J Clin Invest 99:1453-9
Ayus, J C; Arieff, A I (1997) Glycine-induced hypo-osmolar hyponatremia. Arch Intern Med 157:223-6

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