Hypoxic-ischemic brain injury in the neonate remains an important neurological problem. To develop rational designs for prevention and treatment of potentially devastating brain injury, it is essential to understand unique aspects of the regulation of cerebral blood flow in the neonate under various physiological and pathological conditions. The central hypothesis of this proposal is that in the neonate, adenosine is a chemical factor linking cerebral blood flow and metabolism. Our long-term goals are to gain clearer insight into cerebrovascular physiology of the neonate and to define the role of adenosine in the regulation of CBF in the neonate.
Our specific aims are 1) to investigate whether an increase in brain interstitial adenosine during hypoxia is causally related to an increase in CBF in the neonate; 2) to determine the effects of systemic hypotension on regional brain interstitial adenosine concentrations and CBF in the neonate; 3) to examine the role of adenosine in vasodilator response to somatosensory activation in the neonate; 4) to study the role of adenosine in the regulation of CBF during seizures in the neonate. Adenosine will be assayed using the improved fluorescence technique that allows measurement of adenosine at a concentration of as low as 42x10-15 M. The brain dialysis cannula will be utilized to concomitantly measure interstitial fluid adenosine concentration and local CBF in the same area of the brain. The hydrogen clearance will be analyzed to measure CBF using the brain dialysis cannula. In addition, the microsphere technique will be used to measure regional CBF. The cranial window technique will be used to examine the diameters of the pial arterioles.
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