In the neonate, hypoglycemia and hypoxia-ischemia remain the most important causes of brain injury. To develop an effective method to prevent the resultant brain injury, knowledge of the biochemical and physiological derangements unique to the individual disorders is essential. Hypoglycemia in human neonates often occurs together with hypoxia (hypoxic hypoglycemia) or hypotension (hypotensive hypoglycemia). Previous studies have investigated the biochemical derangements that occur during hypoxic or hypotensive hypoglycemia. In contrast, no study thus far has focused on the regulation and alteration of neonatal cerebral blood flow (CBF) during hypoxic or hypotensive hypoglycemia. The piglet hypoglycemia model that we developed offers an excellent in vivo model to study the regulation of CBF during neonatal hypoglycemia. Our hypotheses and research aims are to determine if changes in interstitial fluid concentrations of adenosine during hypoxic and hypotensive hypoglycemia are causally related to changes in blood flow in the neonatal brain, and to elucidate the role of adenosine in postischemic/hypoglycemic hyperemia and hypoperfusion. Our novel modified brain dialysis technique permits simultaneous measurements of interstitial fluid adenosine concentrations and local CBF in the same area of the brain during hypoglycemia. Computerized image analyses of pial arterioles permit examination of temporal changes of pial arterioles in response to administration of adenosine antagonists and agonists during hypoglycemia. CBF measurements with the (14)C- iodoantipyrine autoradiography permit studies of regional CBF during hypoglycemia. Thus, utilization of these three powerful techniques will allow us to thoroughly examine the participation of adenosine in the regulation of CBF during hypoxic and hypotensive hypoglycemia and during postischemic/hypoglycemic reperfusion in the neonate.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021045-11
Application #
2264033
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-07-01
Project End
1995-06-30
Budget Start
1994-07-01
Budget End
1995-06-30
Support Year
11
Fiscal Year
1994
Total Cost
Indirect Cost
Name
Washington University
Department
Neurosurgery
Type
Schools of Medicine
DUNS #
062761671
City
Saint Louis
State
MO
Country
United States
Zip Code
63130
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Park, T S; Gonzales, E R; Shah, A R et al. (1995) Hypoglycemia selectively abolishes hypoxic reactivity of pial arterioles in piglets: role of adenosine. Am J Physiol 268:H871-8
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Ruth, V J; Park, T S; Gonzales, E R et al. (1993) Adenosine and cerebrovascular hyperemia during insulin-induced hypoglycemia in newborn piglet. Am J Physiol 265:H1762-8

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