Reoxygenation stress on blood-brain barrier paracellular permeability and edema in the rat

Ken A. Witt, Karen S. Mark, Karin E. Sandoval, Thomas P. Davis

Research output: Contribution to journalArticlepeer-review

55 Scopus citations


The blood-brain barrier (BBB) serves as a critical regulator of brain homeostasis. Following hypoxia (i.e. 6% oxygen/1 h) and reoxygenation (H/R), the BBB tight junctional complex is disrupted, resulting in increased BBB permeability and the development of vasogenic brain edema. In this study, we examined the effect of H/R on the in vivo rat BBB over a 36 h time course in conjunction with paracellular permeability, gray matter edema, and systemic inflammatory activity. A biphasic increase was observed in the brain uptake of 14C-sucrose, a paracellular permeability marker; with the first increase at the 10 min reoxygenation time point, and the second increase at the 6-18 h time points. Increased brain water weight gain (edema) also showed a biphasic response with the first increase at the 10 min-1 h reoxygenation time points; and the second increase at only the 24 h time point. Analysis of serum derived cytokines (IL-1β, TNFα, IL-6, IL-10, and IFNγ) demonstrated that only IL-1β and IL-6 were at detectable levels, but these levels were similar to controls. White blood cell counts showed significant decreases in lymphocytes (10 min-3 h), increases in monocytes (10 min-3 h and 12 h), and increases in polymorphonuclear cells (1 h and 3 h). We have shown that H/R elicits a biphasic increase in paracellular permeability and edema, which parallel to post-stroke sequelae, despite the lack of occlusion or complete depletion of oxygen.

Original languageEnglish (US)
Pages (from-to)91-96
Number of pages6
JournalMicrovascular Research
Issue number1
StatePublished - Jan 2008


  • Biphasic
  • Hypoxia
  • Oxidative stress
  • Tight junction
  • Vasogenic edema

ASJC Scopus subject areas

  • Biochemistry
  • Cardiology and Cardiovascular Medicine
  • Cell Biology


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