Blood-brain barrier dysfunction developed during normal aging is associated with inflammation and loss of tight junctions but not with leukocyte recruitment

Immunity & Ageing : I & a
Mina ElahyRyusuke Takechi

Abstract

Functional loss of blood-brain barrier (BBB) is suggested to be pivotal to pathogenesis and pathology of vascular-based neurodegenerative disorders such as Alzheimer's disease. We recently reported in wild-type mice maintained on standard diets, progressive deterioration of capillary function with aging concomitant with heightened neuroinflammation. However, the mice used in this study were relatively young (12 months of age) and potential mechanisms for loss of capillary integrity were not investigated per se. The current study therefore extended the previous finding to investigate the effect of aging on BBB integrity in aged mice at 24 months and its potential underlying molecular mechanisms. Immunomicroscopy analyses confirmed significantly increased capillary permeability with heightened neuroinflammation in naturally aged 24-month old mice compared to young control at 3 months of age. Aged mice showed significant attenuation in the expression of BBB tight junction proteins, occludin-1 and to lesser extent ZO-1 compared to young mice. In addition, TNF-α in cerebral endothelial cells of aged mice was significantly elevated compared to controls and this was associated with heightened peripheral inflammation. The expression of...Continue Reading

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Methods Mentioned

BETA
confocal microscopy
flow cytometry
Flow
confocal immunomicroscopy
FACS

Software Mentioned

Volocity
Treestar
FlowJo
GraphPad Prism

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