Barbara Stonestreet

Professor
Pediatrics M.D., Tufts University, 1972
401.274.1122 x1229

Women & Infants' Hospital of Rhode Island
101 Dudley Street
Providence, RI 02905

Research Summary

We have had a long standing interest in fetal and neonatal cerebral circulation. Our recent work focuses on the effect of antenatal steroids on brain maturation. The importance of the hypothalamic-pituitary-adrenocortical axis in the transition to extrauterine life is well-known. This axis potentially also exerts regulatory influences upon the developing central nervous system (CNS). Recent evidence that antenatal corticosteroid (steroid) therapy for fetal maturation reduces the incidence of intraventricular hemorrhage supports the contention that this axis is important in CNS maturation. Nevertheless, the effects of antenatal steroids on the developing CNS have not been well documented. Our work examines the hypotheses that antenatal steroids mature physiologic and improve pathophysiologic cerebrovascular and CNS development. Physiologic, histologic, biochemical and molecular methods are combined in the following Specific Aims: Aim 1 examines the effect of antenatal steroids on blood-brain barrier (BBB) function in (a) normal and (b) osmotically stressed fetal and newborn lambs. Aim 2 examines the effect of steroid pretreatment on brain volume regulation in fetal, newborn, and adult sheep. Aim 3 correlates the effects of steroid pretreatment on Na+,K+-ATPase activity and 1 and 1 isoform gene expression in brain tissue and choroid plexus with brain volume regulation in Aim 2. This enzyme is examined because it maintains normal ion and water homeostasis, and, hypothetically, CNS volume regulation. Aim 4a examines the potential neuroprotective effects of antenatal steroids on CNS ischemia in the fetus. Aim 4b examines the effect of antenatal steroids on Na+,K+-ATPase activity and gene expression in ischemic and normal brain, as in Aim 3.

Selected Publications

Stonestreet, B.S., Patlak, C.S., Pettigrew, K.D., Reilly, C.B. and Cserr, H.F. Ontogeny of blood- brain barrier function in ovine fetuses, lambs and adults. Am. J. Physiol. 71 (Regulatory Integrative Comp. Physiol. 40):R1594-R1601, 1996.
Kim, C.R., Oh, W., and Stonestreet, B.S. Magnesium is a cerebrovasodilator in newborn piglets. Am. J. Physiol. 272 (Heart Circ. Physiol. 41):H511-H516, 1997.
Coyle, M.G., Oh, W., Petersson, K.H., and Stonestreet, B.S. Effects of indomethacin on brain blood flow, cerebral metabolism and sagittal sinus prostanoids after hypoxia. Am. J. Physiol. 269 (Heart Circ. Physiol. 38):H1450-H1459, 1995.

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