Post-ischemic leakiness of the blood-brain barrier: a quantitative and systematic assessment by Patlak plots

Exp Neurol. 2009 Sep;219(1):328-33. doi: 10.1016/j.expneurol.2009.06.002. Epub 2009 Jun 9.

Abstract

The Patlak plot analysis of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) allows estimation of blood-brain barrier (BBB) leakage following temporary focal cerebral ischemia. Thus far, a systematic and quantitative in vivo evaluation of post-ischemic BBB leakage is lacking. Here, using DCE-MRI and the Patlak plot method, we quantitatively assessed BBB leakage in rats at the following time-points after reperfusion: 25 min, 2, 4, 6, 12, 18, 24, 36, 48, and 72 h, and 1, 2, 3, 4, and 5 weeks. Sham-operated animals served as controls. Data collected for each time-point were: the blood-to-brain transfer rate constant (K(i)) of the contrast agent gadolinium, distribution volume (V(p)), ischemic lesion volume, and apparent diffusion coefficient (ADC) values. Compared to controls, K(i), measured at all time-points, except for 5 weeks, appeared significantly different (p<0.001). At several time-points (25 min, 48 and 72 h, 4 and 5 weeks), V(p) was similar compared to that of controls, but for the remaining groups the difference was significant (p<0.001). Analyzing the relationship of K(i) values to time-points, we observed a trend towards a decrease over time (r=-0.61, p=0.014). Both ADC values (r=-0.58, p=0.02) and ischemic lesion volumes (r=0.75, p=0.0015) correlated with K(i) values. These results suggest that after ischemia-reperfusion in rats, BBB leakage is continuous during a 4-week period. Its magnitude diminishes over time and correlates with severity and extent of ischemic injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Brain Barrier / pathology*
  • Blood-Brain Barrier / physiopathology*
  • Brain Edema / etiology
  • Brain Edema / pathology*
  • Brain Edema / physiopathology*
  • Brain Ischemia / complications
  • Brain Ischemia / pathology*
  • Cerebrovascular Circulation / physiology
  • Contrast Media
  • Disease Progression
  • Gadolinium
  • Image Interpretation, Computer-Assisted / methods
  • Infarction, Middle Cerebral Artery / pathology
  • Infarction, Middle Cerebral Artery / physiopathology
  • Laser-Doppler Flowmetry
  • Magnetic Resonance Imaging / methods*
  • Male
  • Rats
  • Rats, Wistar
  • Recovery of Function / physiology
  • Reperfusion Injury / pathology
  • Reperfusion Injury / physiopathology
  • Time Factors

Substances

  • Contrast Media
  • Gadolinium