Ultrastructural analysis of blood-brain barrier breakdown in the peri-infarct zone in young adult and aged mice

作者：Nahirney Patrick C; Reeson Patrick; Brown Craig E^*

来源：Journal of Cerebral Blood Flow and Metabolism, 2016, 36(2): 413-425.

DOI：10.1177/0271678X15608396

• Stroke
• blood-brain barrier
• ischemia
• extravasation
• endothelium
• pericytes
• astrocytes
• basement membrane
• transcytosis
• aging

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.

• 出版日期2016-2