期刊
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
卷 36, 期 2, 页码 413-425出版社
SAGE PUBLICATIONS INC
DOI: 10.1177/0271678X15608396
关键词
Stroke; blood-brain barrier; ischemia; extravasation; endothelium; pericytes; astrocytes; basement membrane; transcytosis; aging
资金
- Heart and Stroke Foundation of BC and Yukon
- CIHR
- MSFHR
- CFI
- NSERC Discovery Grant
- CFI award
Following ischemia, the blood-brain barrier is compromised in the peri-infarct zone leading to secondary injury and dysfunction that can limit recovery. Currently, it is uncertain what structural changes could account for blood-brain barrier permeability, particularly with aging. Here we examined the ultrastructure of early and delayed changes (3 versus 72 h) to the blood-brain barrier in young adult and aged mice (3-4 versus 18 months) subjected to photothrombotic stroke. At both time points and ages, permeability was associated with a striking increase in endothelial caveolae and vacuoles. Tight junctions were generally intact although small spaces were detected in a few cases. In young mice, ischemia led to a significant increase in pericyte process area and vessel coverage whereas these changes were attenuated with aging. Stroke led to an expansion of the basement membrane region that peaked at 3 h and partially recovered by 72 h in both age groups. Astrocyte endfeet and their mitochondria were severely swollen at both times points and ages. Our results suggest that blood-brain barrier permeability in young and aged animals is mediated by transcellular pathways (caveolae/vacuoles), rather than tight junction loss. Further, our data indicate that the effects of ischemia on pericytes and basement membrane are affected by aging.
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