Translational Stroke Research

, Volume 5, Issue 1, pp 3–16

Disruption of Ion Homeostasis in the Neurogliovascular Unit Underlies the Pathogenesis of Ischemic Cerebral Edema

Original Article

DOI: 10.1007/s12975-013-0307-9

Cite this article as:
Khanna, A., Kahle, K.T., Walcott, B.P. et al. Transl. Stroke Res. (2014) 5: 3. doi:10.1007/s12975-013-0307-9


Cerebral edema is a major cause of morbidity and mortality following ischemic stroke, but its underlying molecular pathophysiology is incompletely understood. Recent data have revealed the importance of ion flux via channels and transporters expressed in the neurogliovascular unit in the development of ischemia-triggered cytotoxic edema, vasogenic edema, and hemorrhagic conversion. Disruption of homeostatic mechanisms governing cell volume regulation and epithelial/endothelial ion transport due to ischemia-associated energy failure results in the thermodynamically driven re-equilibration of solutes and water across the CSF–blood and blood–brain barriers that ultimately increases the brain’s extravascular volume. Additionally, hypoxia, inflammation, and other stress-triggered increases in the functional expression of ion channels and transporters normally expressed at low levels in the neurogliovascular unit cause disruptions in ion homeostasis that contribute to ischemic cerebral edema. Here, we review the pathophysiological significance of several molecular mediators of ion transport expressed in the neurogliovascular unit, including targets of existing FDA-approved drugs, which might be potential nodes for therapeutic intervention.


Blood–brain barrier Stroke Ischemia SUR1 Glyburide Bumetanide Ion channel Edema NKCC1 Tumor Hemorrhage TRPM4 Hypertonic 

Copyright information

© Springer Science+Business Media New York 2013

Authors and Affiliations

  • Arjun Khanna
    • 1
    • 2
  • Kristopher T. Kahle
    • 1
    • 2
  • Brian P. Walcott
    • 1
    • 2
  • Volodymyr Gerzanich
    • 3
  • J. Marc Simard
    • 4
  1. 1.Harvard Medical SchoolBostonUSA
  2. 2.Department of NeurosurgeryMassachusetts General HospitalBostonUSA
  3. 3.Department of NeurosurgeryUniversity of Maryland School of MedicineBaltimoreUSA
  4. 4.Departments of Neurosurgery, Pathology, and PhysiologyUniversity of Maryland School of MedicineBaltimoreUSA

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