Stroke-induced blood-brain barrier breakdown along the vascular tree - No preferential affection of arteries in different animal models and in humans.
Stroke-induced blood-brain barrier breakdown promotes complications like cerebral edema and hemorrhagic transformation, especially in association with therapeutical recanalization of occluded vessels. As arteries, capillaries and veins display distinct functional and morphological characteristics, we here investigated patterns of blood-brain barrier breakdown for each segment of the vascular tree in rodent models of embolic, permanent, and transient middle cerebral artery occlusion, added by analyses of human stroke tissue. Twenty-four hours after ischemia induction, loss of blood-brain barrier function towards FITC-albumin was equally observed for arteries, capillaries, and veins in rodent brains. Noteworthy, veins showed highest ratios of leaky vessels, whereas capillaries exhibited the most and arteries the least widespread perivascular tracer extravasation. In contrast, human autoptic stroke tissue exhibited pronounced extravasations of albumin around arteries and veins, while the pericapillary immunoreactivity appeared only faint. Although electron microscopy revealed comparable alterations of the arterial and capillary endothelium throughout the applied animal models, structural loss of arterial smooth muscle cells was only observed in the translationally relevant model of embolic middle cerebral artery occlusion. In light of the so far available concepts of stroke treatment, the consideration of a differential vascular pathophysiology along the cerebral vasculature is likely to allow development of novel effective treatment strategies.
1 Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Martin
M
Krueger
2 Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
Wolfgang
W
Härtig
3 Department of Neuropathology, University Hospital Leipzig, Leipzig, Germany.
Clara
C
Frydrychowicz
3 Department of Neuropathology, University Hospital Leipzig, Leipzig, Germany.
Wolf C
WC
Mueller
2 Paul Flechsig Institute for Brain Research, University of Leipzig, Leipzig, Germany.
Andreas
A
Reichenbach
1 Institute of Anatomy, University of Leipzig, Leipzig, Germany.
Ingo
I
Bechmann
4 Department of Neurology, University Hospital Leipzig, Germany.
Dominik
D
Michalski
D000818:Animals; D001812:Blood-Brain Barrier / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000648:ultrastructure*; D002196:Capillaries / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000648:ultrastructure*; D002536:Cerebral Arteries / Q000000981:diagnostic imaging / Q000503:physiopathology / Q000648:ultrastructure*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008297:Male; D051379:Mice; D008854:Microscopy, Electron; D008856:Microscopy, Fluorescence; D017208:Rats, Wistar; D013045:Species Specificity; D020521:Stroke / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology
Blood–brain barrier; endothelium; focal ischemia; neurovascular unit; stroke
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