title: Post-ischemic blood-brain barrier leakage in rats: one-week follow-up by MRI.
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 (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.
authors.affiliation: Department of Neurology, Helsinki University Central Hospital, Helsinki, Finland. aysan.durukan@hus.fi
authors.forename: Aysan
authors.initials: A
authors.lastname: Durukan
authors.forename: Ivan
authors.initials: I
authors.lastname: Marinkovic
authors.forename: Daniel
authors.initials: D
authors.lastname: Strbian
authors.forename: Miia
authors.initials: M
authors.lastname: Pitkonen
authors.forename: Eric
authors.initials: E
authors.lastname: Pedrono
authors.forename: Lauri
authors.initials: L
authors.lastname: Soinne
authors.forename: Usama
authors.initials: U
authors.lastname: Abo-Ramadan
authors.forename: Turgut
authors.initials: T
authors.lastname: Tatlisumak
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D001794:Blood Pressure; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D001831:Body Temperature; D001921:Brain / Q000473:pathology / Q000503:physiopathology; D002545:Brain Ischemia / Q000150:complications* / Q000473:pathology; D002199:Capillary Permeability; D005500:Follow-Up Studies; D005682:Gadolinium; D020244:Infarction, Middle Cerebral Artery / Q000150:complications* / Q000473:pathology; D008279:Magnetic Resonance Imaging; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D015427:Reperfusion Injury / Q000150:complications* / Q000473:pathology; D013997:Time Factors
chemical_list: D005682:Gadolinium