http://jcb.sagepub.com/content/early/2016/01/28/0271678X16629976.full
- Catherine B Lawrence, Faculty of Life Sciences, The University of Manchester, AV Hill Building, Oxford Road, Manchester M13 9PT, UK. Email: catherine.lawrence@manchester.ac.uk
Abstract
Blood–brain barrier breakdown worsens ischaemic damage, but it is unclear how molecules breach the blood–brain barrier in vivo.
Using the obese ob/ob mouse as a model of enhanced blood–brain barrier breakdown, we investigated how stroke-induced structural changes to the
microvasculature related to blood–brain barrier permeability. Ob/ob
mice underwent middle cerebral artery occlusion, followed by 4 or 24 h
reperfusion. Blood–brain barrier integrity was assessed
using IgG and horseradish peroxidase staining, and
blood–brain barrier structure by two-dimensional and three-dimensional
electron microscopy. At 4 and 24 h post-stroke, ob/ob mice had increased ischaemic damage and blood–brain barrier breakdown compared to ob/– controls, and vessels from both genotypes showed astrocyte end-foot swelling and increased endothelial vesicles. Ob/ob
mice had significantly more endothelial vesicles at 4 h in the
striatum, where blood–brain barrier breakdown was most severe.
Both stroke and genotype had no effect on tight
junction structure visualised by electron microscopy, or protein
expression
in isolated microvessels. Astrocyte swelling
severity did not correlate with tissue outcome, being unaffected by
genotype
or reperfusion times. However, the rare instances
of vessel lumen collapse were always associated with severe astrocyte
swelling
in two-dimensional and three-dimensional electron
microscopy. Endothelial vesicles were therefore the best spatial and
temporal
indicators of blood–brain barrier breakdown after
cerebral ischaemia.
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