Using the newborn piglet model, hypoglycemia (blood glucose concentration 1 mmol/L for 2 hr) will be induced using an insulin infusion and the glucose clamp technique. Brain tissue will be obtained at various time points between 0 hr and 7 days after exposure to hypoglycemia. The proposed studies will 1) quantitate hypoglycemia-induced free-radical mediated changes in mitochondrial proteins, lipids, and DNA, and demonstrate the mitochondrial specificity of increased free radical production; 2) assess the effect of hypoglycemia on mitochondrial function by measuring mitochondrial calcium uptake and activity of electron transport chain enzymes; 3) establish the role of the antioxidants glutathione and superoxide dismutase and the pro-oxidants nitric oxide and peroxynitrate in mediating hypoglycemia-induced cerebral mitochondrial oxidant injury; and 4) correlate the effects of hypoglycemia-induced alterations in mitochondrial structure and function with neurochemical, immunohistochemical, and morphologic evidence of altered neuronal structure and function with neurochemical, immunohistochemical, and morphologic evidence of altered neuronal structure and cell death.

Agency
National Institute of Health (NIH)
Institute
Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Type
Research Project (R01)
Project #
5R01HD042071-02
Application #
6536443
Study Section
Human Embryology and Development Subcommittee 1 (HED)
Program Officer
Oster-Granite, Mary Lou
Project Start
2001-07-01
Project End
2004-06-30
Budget Start
2002-07-01
Budget End
2003-06-30
Support Year
2
Fiscal Year
2002
Total Cost
$257,513
Indirect Cost
Name
Johns Hopkins University
Department
Pediatrics
Type
Schools of Medicine
DUNS #
045911138
City
Baltimore
State
MD
Country
United States
Zip Code
21218