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Morphometric analysis of the blood‐brain barrier in the peri‐infarct zone in young adult and aged mice
Author(s) -
Nahirney Patrick C,
Reeson Patrick,
Brown Craig E
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.30.1_supplement.562.5
Subject(s) - blood–brain barrier , extravasation , basement membrane , tight junction , transcellular , vacuole , evans blue , pathology , ischemia , pericyte , biology , microglia , medicine , inflammation , endocrinology , microbiology and biotechnology , endothelial stem cell , central nervous system , cytoplasm , in vitro , biochemistry
After an ischemic stroke, the blood brain barrier (BBB) is compromised in the peri‐infarct zone leading to secondary injury and neuronal dysfunction that can limit brain recovery. There is uncertainty what accounts for an increase in BBB permeability in capillaries of peri‐infarct tissues, particularly in aged animals. We utilized electron microscopy to study early (3 h) and late (72 h) changes to the BBB in young (3–4 mo) adult and aged (18 mo) mice after photothrombotic stroke. In all groups, peri‐infarct BBB permeability (as determined by Evans blue extravasation) was accompanied by endothelial swelling and an increase in transcytotic vesicles and vacuoles. In flowing capillaries, tight junctions (TJ) between endothelial cells were intact although small gaps were detected in a fraction of cases. In young adult mice (but not old mice) there was a marked increase in pericyte size and coverage of the capillaries. In both groups, thickening of the underlying basement membrane of capillaries peaked at 3 h and partially recovered by 72 h in young but not aged mice. Surrounding astrocytes and their mitochondria were severely swollen at both times points and ages. At 72 h, astrocytes were filled with glycogen deposits suggesting an upregulation of energy storage. These data suggest that BBB permeability in the peri‐infarct cortex of young adult and aged animals is likely mediated by transcellular pathways rather than TJ disruption. Additionally, our results indicate that pericyte and basement membrane responses to ischemia are affected by aging. Support or Funding Information Heart and Stroke Foundation of BC and Yukon, CIHR, MSFHR, CFI, NSERC