Blood-brain barrier permeability to manganese and to Gd-DOTA in a rat model of transient cerebral ischaemia.
Loss of integrity of the blood-brain barrier (BBB) and brain swelling is a potentially lethal complication of reperfusion in human stroke. To assess the time course of BBB modifications, we performed angiography, diffusion-weighted imaging, T1-weighted (T1 W) imaging and T1 mapping, and monitored acute changes after middle cerebral artery occlusion and recanalization in rats (n = 27). The animals were grouped according to the duration of occlusion: 30 min (group A, n = 8), 1 h 30 min (group B, n = 9), and 2 h 30 min (group C, n = 10). For 17 animals (four in group A, six in group B, and seven in group C), MnCl2 and dimeglumine gadoterate (Gd-DOTA) were injected at 13 min and 34 min after recanalization, respectively. The 10 remaining animals (control groups) underwent the same acquisition protocols, but no contrast agents were injected. Cell damage was determined 1 h after recanalization on haematoxylin and eosin-stained sections. Our results indicate that in the middle cerebral artery occlusion model in the rat, changes in BBB permeability assessed by contrast agent extravasation occur within the first hour of reperfusion, even after an occlusion period not exceeding 30 min. No differences between BBB permeability to Gd-DOTA and Mn2+ were detected in our experimental conditions. The reduction in apparent diffusion coefficient during occlusion appears to be a good predictor of BBB modifications after reperfusion in this model.
Grillon
Emmanuelle
E
Inserm, U836, Grenoble F-38043, France. emmanuelle.grillon@ujf-grenoble.fr
Provent
Peggy
P
Montigon
Olivier
O
Segebarth
Christoph
C
Rémy
Chantal
C
Barbier
Emmanuel L
EL
D000818:Animals; D001812:Blood-Brain Barrier / Q000503:physiopathology*; D002199:Capillary Permeability; D002533:Cerebral Angiography; D003287:Contrast Media / Q000493:pharmacokinetics; D038524:Diffusion Magnetic Resonance Imaging; D004195:Disease Models, Animal; D006571:Heterocyclic Compounds / Q000493:pharmacokinetics*; D020244:Infarction, Middle Cerebral Artery / Q000503:physiopathology; D002546:Ischemic Attack, Transient / Q000503:physiopathology*; D008297:Male; D008345:Manganese / Q000493:pharmacokinetics*; D009942:Organometallic Compounds / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015424:Reperfusion; D015427:Reperfusion Injury / Q000503:physiopathology; D013997:Time Factors
D003287:Contrast Media; D006571:Heterocyclic Compounds; D009942:Organometallic Compounds; D008345:Manganese; C050823:gadolinium 1,4,7,10-tetraazacyclododecane-N,N',N'',N'''-tetraacetate