Hypoxic brain injury is the most important neurological problem during the perinatal period. However, lack of information on cerebral blood flow (CBF) and its regulation in the postnatal period has prevented clear understanding of the pathogenesis of this condition. The overall goal of this proposal is to gain insight into the metabolic regulation of CBF in the postnatal period and to define the role of adenosine in linking brain metabolism and CBF at this developmental stage.
Our specific aims are 1) to investigate whether exogenous adenosine produces cerebral vasodilation and increase in CBF in the newborn; 2) to examine the role of adenosine in vasodilatory response to photic stimulation in the neonatal brain; 3) to determine if the adenosine level rises to produce vasodilation in the neonatal brain during hypoxia; 4) to determine the effect of systemic hypotension on the regional brain adenosine level and the role of adenosine in selective sparing of gray matter flow during severe systemic hypotension in the newborn. CBF will be measured by the radioactive microsphere technique. The brain microdialysis technique will be employed in detecting the interstitial fluid adenosine level. Adenine nucleosides and nucleotides will be measured by HPLC techniques.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
5R01NS021045-03
Application #
3401783
Study Section
Neurology A Study Section (NEUA)
Project Start
1985-07-01
Project End
1988-06-30
Budget Start
1987-07-01
Budget End
1988-06-30
Support Year
3
Fiscal Year
1987
Total Cost
Indirect Cost
Name
University of Virginia
Department
Type
Schools of Medicine
DUNS #
001910777
City
Charlottesville
State
VA
Country
United States
Zip Code
22904
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Altay, Tamer; McLaughlin, Bethann; Wu, Jane Y et al. (2007) Slit modulates cerebrovascular inflammation and mediates neuroprotection against global cerebral ischemia. Exp Neurol 207:186-94
Gidday, Jeffrey M; Gasche, Yvan G; Copin, Jean-C et al. (2005) Leukocyte-derived matrix metalloproteinase-9 mediates blood-brain barrier breakdown and is proinflammatory after transient focal cerebral ischemia. Am J Physiol Heart Circ Physiol 289:H558-68
Zhang, Yunhong; Zhang, Xiaochun; Park, Tae S et al. (2005) Cerebral endothelial cell apoptosis after ischemia-reperfusion: role of PARP activation and AIF translocation. J Cereb Blood Flow Metab 25:868-77
Hill, M W; Wong, M; Amarakone, A et al. (2000) Rapid cooling aborts seizure-like activity in rodent hippocampal-entorhinal slices. Epilepsia 41:1241-8
Gidday, J M; Kim, Y B; Shah, A R et al. (1996) Adenosine transport inhibition ameliorates postischemic hypoperfusion in pigs. Brain Res 734:261-8
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
Kim, Y B; Gidday, J M; Gonzales, E R et al. (1994) Effect of hypoglycemia on postischemic cortical blood flow, hypercapnic reactivity, and interstitial adenosine concentration. J Neurosurg 81:877-84
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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