Recent/Current
Research Funding

National Institute
of Health

American Diabetes Association

Graduate Group Affiliations

Molecular, Cellular and
Integrated Physiology

Biochemistry, Molecular, Cellular and Developmental
Biology

Research Interests

Brain microvascular endothelial cell and astrocyte Na transporters in cerebral edema formation during ischemic stroke and diabetic ketoacidosis.

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 roles of Na transporters, including Na-K-Cl cotransport, Na/H exchange and Na/HCO3 cotransport 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 diabetic conditions on ion transport processes of blood brain barrier endothelial cells and astrocytes; and 3) brain microvascular endothelial cell and astrocyte pathophysiology in diabetic ketoacidosis (DKA). We use a variety of experimental methods, including cell culture and microvessel isolation, protein biochemistry, molecular biology, confocal microscopy immunofluorescence, immunoelectron microscopy and nuclear magnetic resonance imaging and spectroscopy.

 

Representative 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. pmid:15356425.

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. PMID: 15677509.

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. PMID: 15800057.

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. PMID: 16079189.

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 26: 1234-1249. PMID: 16421506.

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 291: R1-R25. PMID: 16484438.

2007  Brillault, J., T.I. Lam, J.M. Rutkowsky, S. Foroutan and M.E. O’Donnell. Hypoxia effects on cell volume and ion uptake of cerebral microvascular endothelial cells. American Journal of Physiology: Cell Physiology 294: C88-C96. PMID: 17942640.

2007  Chang, E., M.E. O’Donnell and A.I. Barakat. Shear stress and 17b-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels. American Journal of Physiology: Cell Physiology 294: C363-C371. PMID: 17959724.

2008  Yuen, N., S.E. Anderson, N. Glaser, D.J. Tancredi and M.E. O’Donnell. Cerebral blood flow and cerebral edema in rats with diabetic ketoacidosis. Diabetes 57: 2588-2594. PMCID: PMC2551666.

2008  M.E. O’Donnell. Ion Transport. In: A. Kastin and W. Pan, eds., The Blood-Brain Barrier: Understanding the Regulatory Gatekeeper Between Brain and Body, Henry Stewart Talks Ltd, London., online publication (http://www.hstalks.com/?t=BL0381727-ODonnell).

2009  M.E. O’Donnell. Ion and water transport across the blood-brain barrier. In: F.J. Alvarez-Leefmans and E. Delpire, eds, Physiology and Pathophysiology of Chloride Transporters and Channels in the Nervous System: From Molecular to Diseases. Elsevier-Academic Press, San Diego, CA, pp 585-606.

2009  Lam, T.I., P.M. Wise and M.E. O’Donnell. Cerebral microvascular endothelial cell Na/H exchange: evidence for the presence of NHE1 and NHE2 isoforms and regulation by arginine vasopressin. American Journal of Physiology: Cell Physiology 297: C278-C289. PMCID: PMC2724093.

2009  Glaser, N., N. Yuen, S.E. Anderson, D.J. Tancredi and M.E. O’Donnell. Cerebral metabolic alterations in rats with diabetic ketoacidosis: effects of treatment with insulin and intravenous fluids and effects of bumetanide. Diabetes 59:702-709. PMCID: PMC2828650.

2011  Neuwelt, E.A., B. Bauer, C. Fahlke, G. Fricker, C. Iadecola, D. Janigro, L. Leybaert, Z. Molnar, *M. O’Donnell, J. Povlishock, N. Saunders, F. Sharp, D. Stanimirovic, R. Watts and *L. Drewes. Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology. Nature Reviews Neuroscience 12: 169-182. PMID:21331083.

2011  M. O’Donnell, R. Daneman, M.J. Fisher, L.J. Noble, B.R. Ransom, B.J. Spencer and F. Sharp. Molecular Physiology of the Brain and Brain Barriers Working Group Report. Online Supplement to Engaging Neuroscience to Advance Translational Research in Brain Barrier Biology. Nature Reviews Neuroscience 12: 169-182. www.nature.com/reviews/neuro

2011  Rutkowsky, J.M., B.K. Wallace, P.M. Wise and M.E. O’Donnell. Effects of estradiol on ischemic factor-induced astrocyte swelling and AQP4 protein abundance. American Journal of Physiology Cell Physiology, doi:10.1152/ajpcell.00399.2010. PMID: 21471464.

2011  Wallace, B.K., S. Foroutan and M.E. O’Donnell. Ischemia-Induced stimulation of Na-K-Cl Cotransport in cerebral microvascular endothelial cells involves AMP kinase, American Journal of Physiology Cell Physiology, doi:10.1152/ajpcell.00517.2010. PMID: 21562306.

2011  Chen, Y.-J., G. Raman, S. Bedendiek, M.E. O’Donnell and H. Wulff. The KCa3.1 blocker TRAM-34 reduces infarction and neurological deficit in a rat model of ischemia/reperfusion stroke, Journal of Cerebral Blood Flow and Metabolism, doi: 10.1038/jcbfm.2011.101. PMID: 21750563.

2012  Wallace, B.K., K. Jelks and M.E. O’Donnell. Ischemia-Induced stimulation of Na- K-Cl Cotransport in cerebral microvascular endothelial cells: role of p38 and JNK MAP kinases, American Journal of Physiology Cell Physiology, 302: C505-C517  PMCID: PMC3287160.

2012  Glaser, N., S. Anderson, W. Leong, D. Tancredi and M. O’Donnell. Cognitive dysfunction associated with diabetic ketoacidosis in rats. Neuroscience Letters 510: 110-114. PMCID: PMC3291100.

2012  Glaser, N., C. Ngo, S. Anderson, N. Yuen, A. Trifu and M. O’Donnell. Effects of hyperglycemia and ketosis on cerebral perfusion, cerebral water distribution and cerebral metabolism. Diabetes 61: 1831-1837 PMID: 22498698. PMCID: PMC3379676.

2012  M.E. O’Donnell, M.E., Y.-J. Chen, T.I. Lam, J. Walton and S.E. Anderson. Intravenous HOE-642 reduces brain edema and Na uptake in the rat middle cerebral artery occlusion model of stroke: evidence for participation of the blood-brain barrier Na/H exchanger, Journal of Cerebral Blood Flow and Metabolism, doi: 10.1038/jcbfm.2012.160 PMID: 23149557

 

Recent/Current Teaching

CHA403, Neurobiology
HPH299, Research
HPH400, Human Physiology
SUR493C/HPH493C, Care of the Critically Ill Surgical Patient
MCP210A, Advanced Physiology

 

Honors and Awards

Established Investigator, American Heart Association
Chair, Molecular and Cellular Physiology Section, American Physiological Society
Editorial Board Member, American Journal of Physiology Cell Physiology
Editorial Board Member, Fluids and Barriers of the CNS
Research Committee, American Heart Association
National Institutes of Health NINDS Brain Injury and Neuropathology Study Section
Past Chair, Barriers of the CNS Gordon Research Conference
Past Chair, Molecular, Cellular and Integrative Physiology Graduate Group, UC Davis
Past-Chair, American Heart Association Grant Review Committee
Co-Chair, American Heart Association Young Investigators Forum