Post-ischemic blood-brain barrier leakage in rats: one-week follow-up by MRI

Blood-brain barrier (BBB) disruption following ischemia-reperfusion is associated with such devastating consequences as edema and hemorrhagic transformation. Although several earlier reports on BBB disruption after experimental focal cerebral ischemia-reperfusion pointed out a biphasic opening, discrepancies occurred among the results of these studies as to the second opening. Furthermore, rarely was any evaluation longitudinal. We therefore performed repeated dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) to monitor BBB permeability to gadopentetate dimeglumine (Gd-DTPA) following 90 min of transient focal cerebral ischemia in a single group of rats (n=10). At five time-points after reperfusion (at 2, 24, 48, 72 h, and 1 week), we estimated the blood-to-brain transfer rate constant (K(i)) of gadolinium with the Patlak plot graphical approach, and calculated contrast enhancement magnitude based on signal intensities of pre- and postcontrast T1-weighted images. Both methods revealed a persistent permeability to gadolinium during the whole experiment. The magnitude of contrast enhancement appeared higher at 1 week than at any of the other time-points (p<0.001), whereas no difference appeared in K(i) estimations when we analyzed the enhancement areas as an entirety. Sub-region K(i) values in a limited cortical area showed a difference at 1 week (p=0.014). The present study confirms that following transient focal cerebral ischemia, BBB leakage to Gd-DTPA is continuous, and during 1 week postreperfusion no BBB closure occurs.