Early blood-brain barrier disruption in human focal brain ischemia

Ann Neurol. 2004 Oct;56(4):468-77. doi: 10.1002/ana.20199.


Loss of integrity of the blood-brain barrier (BBB) resulting from ischemia/reperfusion is believed to be a precursor to hemorrhagic transformation (HT) and poor outcome. We used a novel magnetic resonance imaging marker to characterize early BBB disruption in human focal brain ischemia and tested for associations with reperfusion, HT, and poor outcome (modified Rankin score >2). BBB disruption was found in 47 of 144 (33%) patients, having a median time from stroke onset to observation of 10.1 hours. Reperfusion was found to be the most powerful independent predictor of early BBB disruption (p = 0.018; odds ratio, 4.09; 95% confidence interval, 1.28-13.1). HT was observed in 22 patients; 16 (72.7%) of those also had early BBB disruption (p < 0.001; odds ratio, 8.11; 95% confidence interval, 2.85-23.1). In addition to baseline severity (National Institutes of Health Stroke Scale score >6), early BBB disruption was found to be an independent predictor of HT. Because the timing of the disruption was early enough to make it relevant to acute thrombolytic therapy, early BBB disruption as defined by this imaging biomarker may be a promising target for adjunctive therapy to reduce the complications associated with thrombolytic therapy, broaden the therapeutic window, and improve clinical outcome.

Publication types

  • Comparative Study

MeSH terms

  • Aged
  • Aged, 80 and over
  • Analysis of Variance
  • Blood-Brain Barrier / drug effects
  • Blood-Brain Barrier / physiopathology*
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology*
  • Brain Ischemia / prevention & control
  • Brain Mapping
  • Cerebral Hemorrhage / drug therapy
  • Cerebral Hemorrhage / pathology
  • Cerebral Hemorrhage / physiopathology
  • Chi-Square Distribution
  • Diffusion Magnetic Resonance Imaging / methods
  • Female
  • Follow-Up Studies
  • Gadolinium DTPA / analogs & derivatives*
  • Humans
  • Male
  • Middle Aged
  • Odds Ratio
  • Oleic Acids
  • Predictive Value of Tests
  • Reperfusion / adverse effects
  • Retrospective Studies
  • Statistics, Nonparametric
  • Time Factors
  • Tissue Plasminogen Activator / therapeutic use


  • Oleic Acids
  • gadolinium diethylene-triamine-pentaacetic acid-bis-oleate
  • Tissue Plasminogen Activator
  • Gadolinium DTPA