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

• Published in: Brain research 2009-07, Vol.1280, p.158-165
• Main Authors: Durukan, Aysan, Marinkovic, Ivan, Strbian, Daniel, Pitkonen, Miia, Pedrono, Eric, Soinne, Lauri, Abo-Ramadan, Usama, Tatlisumak, Turgut
• Format: Article
• Language: English
• Subjects: Analysis of Variance; Animals; BBB permeability; Biological and medical sciences; Blood Pressure; Blood-Brain Barrier - physiopathology; Body Temperature; Brain - pathology; Brain - physiopathology; Brain Ischemia - complications; Brain Ischemia - pathology; Capillary Permeability; Cerebral circulation. Blood-brain barrier. Choroid plexus. Cerebrospinal fluid. Circumventricular organ. Meninges; Focal ischemia; Follow-Up Studies; Fundamental and applied biological sciences. Psychology; Gadolinium; Infarction, Middle Cerebral Artery - complications; Infarction, Middle Cerebral Artery - pathology; Magnetic Resonance Imaging; Male; Medical sciences; Middle cerebral artery occlusion; MRI; Neurology; Rat; Rats; Rats, Wistar; Reperfusion; Reperfusion Injury - complications; Reperfusion Injury - pathology; Time Factors; Vascular diseases and vascular malformations of the nervous system; Vertebrates: nervous system and sense organs
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2009.05.025

Abstract 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 ( Ki ) 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 Ki estimations when we analyzed the enhancement areas as an entirety. Sub-region Ki 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.