Acute Leakage Patterns of Fluorescent Plasma Flow Markers after Transient Focal Cerebral Ischemia Suggest Large Openings in Blood‐Brain Barrier
Open Access
- 26 January 2008
- journal article
- Published by Wiley in Microcirculation
- Vol. 15 (1), 1-14
- https://doi.org/10.1080/10739680701409811
Abstract
Objective: This study tested the hypothesis that blood‐brain barrier (BBB) opening during acute reperfusion permits the passage of smaller macromolecules but not larger ones and that this molecular size restriction disappears over time. Methods: Following 3 hours (h) of unilateral middle cerebral artery occlusion and either 3 or 21 h of reperfusion, Wistar rats (n = 42) were injected with Evans blue (EB, a fluorescent dye that binds instantly to plasma albumin yielding EB‐tagged albumin, EB‐Alb) and with one of three fluorescent dextrans ranging in size from 77‐ to 2000‐kDa. During occlusion and reperfusion, ischemic status of the affected tissue was confirmed by magnetic resonance imaging (MRI). Blood‐to‐brain transfer of the dextrans relative to that of EB‐Alb was examined by fluorescence microscopy within three regions with ischemic damage. Results: Increase in EB‐Alb leakage from 3 to 21 h of reperfusion was significant (from 40–60% to 80–90% of fields examined; p < 0.05). Co‐leakage of the largest dextran used 2000‐kDa, with EB‐Alb was observed in only 40% of the fields at 3+3 h, but nearly in all at 3 + 21 h (p < 0.01). Parenchymal distribution of the tracers differed among the fields and included considerable cellular uptake of EB‐Alb and some of dextrans. Conclusions: Supporting the hypothesis, opening of the BBB was insufficient to allow passage of the largest dextran at 3 + 3 h in about 40% of the microvascular networks viewed. The number of total leaky microvascular beds increased by nearly 50% between 3 + 3 h and 3 + 21 h.Keywords
This publication has 37 references indexed in Scilit:
- The Neurotoxicity of Tissue Plasminogen Activator?Journal of Cerebral Blood Flow & Metabolism, 2004
- Sickle red blood cells accumulate in tumorMagnetic Resonance in Medicine, 2003
- Microvascular Basal Lamina Injury after Experimental Focal Cerebral Ischemia and Reperfusion in the RatJournal of Cerebral Blood Flow & Metabolism, 2002
- Matrix Metalloproteinases and TIMPs Are Associated With Blood-Brain Barrier Opening After Reperfusion in Rat BrainStroke, 1998
- Prediction of Impending Hemorrhagic Transformation in Ischemic Stroke Using Magnetic Resonance Imaging in RatsStroke, 1998
- Reperfusion-induced injury to the blood-brain barrier after middle cerebral artery occlusion in rats.Stroke, 1994
- Reversible middle cerebral artery occlusion without craniectomy in rats.Stroke, 1989
- Ischemic brain edema following occlusion of the middle cerebral artery in the rat. I: The time courses of the brain water, sodium and potassium contents and blood-brain barrier permeability to 125I-albumin.Stroke, 1985
- Early changes in blood brain barrier permeability to small molecules after transient cerebral ischemia.Stroke, 1983
- Differential blood-brain barrier permeabilities to [14C]sucrose and [3H]inulin after osmotic opening in the ratExperimental Neurology, 1983