Martha E. O'Donnell, Ph.D.
Professor
4155 Tupper Hall
Davis Campus
530-752-7626
e-mail

Brain microvascular endothelial cell and astrocyte ion transporters and channels in ischemic stroke and diabetes.

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 in vitro and in vivo experimental methods, including cell culture and microvessel isolation, protein biochemistry, molecular biology, confocal microscopy immunofluorescence, immunoelectron microscopy and nuclear magnetic resonance imaging and spectroscopy.

Y.-J. Chen, B.K. Wallace, N. Yuen, D.P. Jenkins, H. Wulff and M.E. O’Donnell. Blood brain barrier KCa3.1 channels: evidence for a role in brain Na uptake and edema in ischemic stroke. Stroke 2015 Jan;46: 237-244 PMCID: PMC4276511

M.E. O’Donnell. The neurovascular unit. In: K. Dorovini-Zis, ed. The Blood-Brain Barrier in Health and Disease. 2015 Science Publishers, Enfield, NH, invited chapter, in press.

M.E. O’Donnell. Blood Brain Barrier Na Transporters in Ischemic Stroke. In: T.P. Davis, ed., Advances in Pharmacology 2014;71, Burlington: Academic Press, pp 113-146 PMID 25407215 [PubMed – in process]. ISBN: 978-0-12-800282-7

Lo, W., M.E. O’Donnell, D. Tancredi, M. Orgain and N. Glaser. Diabetic ketoacidosis in juvenile rats is associated with reactive gliosis and activation of microglia in the hippocampus. Pediatric Diabetes, 2016 Mar;17(2):127-39. doi: 10.1111/pedi.12251. Epub 2015 Jan 16.

Yuen, N., T.I. Lam, B.K. Wallace, N.R. Klug, S.E. Anderson and M.E. O’Donnell. Ischemic factor-induced increases in cerebral microvascular endothelial cell Na/H exchange activity and abundance: evidence for involvement of ERK1/2 MAP kinase. American Journal of Physiology Cell Physiology 2014 May 15;306: C931-C942, PMID: 245647544 PMCID: In process.

Glaser, N., A. Bundros, S. Anderson, D. Tancredi, W. Lo, M. Orgain and M. O’Donnell. Brain swelling during hypocapnia increases with hyperglycemia or ketosis. Pediatric Diabetes, 2014 Nov;15(7):484-93. doi: 10.1111/pedi.12114. Epub 2014 Jan 20.

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 2013 Feb;33: 225-234 PMID: 23149557. PMCID: PMC3564192.

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 2012 Jul;61: 1831-1837 PMID: 22498698. PMCID: PMC3379676.

Glaser, N., S. Anderson, W. Leong, D. Tancredi and M. O’Donnell. Cognitive dysfunction associated with diabetic ketoacidosis in rats. Neuroscience Letters 2012 Feb 29;510: 110-114. PMCID: PMC3291100.

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, 2012 Feb 1;302: C505-C517  PMCID: PMC3287160.

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, 2011 Dec;31(12):2363-74. doi: 10.1038/jcbfm.2011.101. PMID: 21750563.

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, 2011 Aug;301(2):C316-26. doi:10.1152/ajpcell.00517.2010. PMID: 21562306.

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, 2011 Jul;301(1):C204-12. doi:10.1152/ajpcell.00399.2010. PMID: 21471464.

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 2011;12: 169-182. www.nature.com/reviews/neuro

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 2011 Mar;12: 169-182. PMID:21331083.

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 2010 Mar;59:702-709. PMCID: PMC2828650.

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 2009 Aug;297: C278-C289. PMCID: PMC2724093.

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, 2010. pp 585-606.

M.E. O’Donnell. (2008) 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). 

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 2008 Oct;57: 2588-2594. PMCID: PMC2551666.

Chang, E., M.E. O’Donnell and A.I. Barakat. Shear stress and 17β-estradiol modulate cerebral microvascular endothelial Na-K-Cl cotransporter and Na/H exchanger protein levels. American Journal of Physiology: Cell Physiology 2008 Jan;294: C363-C371. PMID: 17959724.

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 2008 Jan;294: C88-C96. PMID: 17942640.

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 2006 Jul;291: R1-R25. PMID: 16484438.

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 2006 Oct;26: 1234-1249. PMID: 16421506.

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 2005 Dec;289: C1492-C1501. PMID: 16079189.

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, 2005 Aug;289: C283-C292. PMID: 15800057.

T. I. Lam, S.E. Anderson, N. Glaser and M. E. O'Donnell. Bumetanide reduces cerebral edema formation in rats with diabetic ketoacidosis. Diabetes 2005 Feb;54: 510-516. PMID: 15677509.

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, 2004 Sep;24: 1046-1056. pmid:15356425.

  • Established Investigator, American Heart Association
  • Editorial Board Member, American Journal of Physiology Cell Physiology
  • Editorial Board Member, Fluids and Barriers of the CNS
  • Research Committee, American Heart Association
  • 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
  • Founding member, International Brain Barriers Society
  • Chair, Molecular and Cellular Physiology Section, American Physiological Society
  • National Institutes of Health NINDS Brain Injury and Neuropathology Study Section (standing member)
  • CHA403, Neurobiology
  • HPH299, Research
  • HPH400, Human Physiology
  • SUR493C/HPH493C, Care of the Critically Ill Surgical Patient
  • MCP210A, Advanced Physiology
  • National Institutes of Health
  • American Diabetes Association
  • American Heart Association