RESEARCH INTERESTS

The role of brain microvascular endothelial cell and astrocyte Na transporters in cerebral edema formation during ischemic stroke and diabetic ketoacidosis.

RESEARCH SYNOPSIS

The primary research focus of my laboratory is on cellular mechanisms of brain water and electrolyte homeostasis in health and disease. In current studies we are investigating 1) the role of the Na-K-Cl cotransporter and Na/H exchanger in normal blood-brain barrier function as well as the pathophysiology of stroke with a special emphasis on ischemia-induced cerebral edema formation; 2) the effects of estrogen on ion transport processes of the brain microvascular endothelial cells and astrocytes; and 3) brain microvascular endothelial cell and astrocyte pathophysiology in diabetic ketoacidosis. We use a variety of experimental methods, including cell culture and microvessel isolation, protein biochemistry, molecular biology, immunoelectron microscopy and nuclear magnetic resonance, including diffusion weighted imaging and localized Na spectroscopy to image water and Na changes in a rat model of ischemic stroke.

SELECTED PUBLICATIONS

2004 O'Donnell, M.E., L. Tran, T. Lam, X.B. Liu and S.E. Anderson. Bumetanide inhibition of the blood-brain barrier Na-K-Cl cotransporter reduces edema formation in the rat middle cerebral artery occlusion model of stroke. Journal of Cerebral Blood Flow and Metabolism, 24: 1046-1056.

2005 T. I. Lam, S.E. Anderson, N. Glaser and M. E. O'Donnell. Bumetanide reduces cerebral edema formation in rats with diabetic ketoacidosis. Diabetes 54: 510-516.

2005 O'Donnell, M.E., V. Duong, S. Suvatne, S. Foroutan, and D. M. Johnson. Arginine vasopressin stimulation of cerebral microvascular endothelial cell Na-K-Cl cotransport activity is V1 receptor- and [Ca]-dependent. American Journal of Physiology, 289: C283-C292. First published March 2005; doi:10.1152/ajpcell.00001.2005.

2005 Foroutan, S., J. Brillault, B. Forbush, and M.E. O'Donnell, Moderate to severe ischemic conditions increase activity and phosphorylation of the cerebral microvascular endothelial cell Na-K-Cl cotransporter. American Journal of Physiology: Cell Physiology 289: C1492-C1501 doi:10.1152/ajpcell.00257.2005.

2005 O'Donnell, M.E., T. I. Lam, L.Q. Tran, S. Foroutan and S.E. Anderson. Estradiol reduces activity of the blood-brain barrier Na-K-Cl cotransporter and decreases edema formation in permanent middle cerebral artery occlusion. Journal of Cerebral Blood Flow and Metabolism doi: 10.1038/sj.jcbfm.9600278.

2005 Tran, L., S.E. Anderson and M.E. O'Donnell. Reduction of cerebral edema by bumetanide administered after initiation of permanent middle cerebral artery occlusion. FASEB J. 19: A808.

2005 Brillault, J. and M.E. O'Donnell. Effects of hypoxia and vasopressin on cerebral microvascular endothelial cell intracellular volume. FASEB J. 19: A809.

2006 Pedersen, S.F., M.E. O'Donnell, S.E. Anderson, and P.M. Cala. Physiology and pathophysiology of Na⁺/H⁺ exchange and Na⁺/K⁺/2Cl^- cotransporter in the heart, brain, and blood. American Journal of Physiology: Regulatory, Integrative and Comparative Physiology doi:10.1152/ajpregu.00782.2005.