Abstract
Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system. Even though the effects of chronic stress on brain system have been extensively studied, there are few in vivo dynamic studies on the effects of chronic stress on the cerebro-vascular system. In this study, the effects of chronic stress on cerebral vasculature and BBB permeability were studied using in vivo two-photon (2p) microscopic imaging with an injection of fluorescence-conjugated dextran. Our real-time 2p imaging results showed that chronic stress reduced the vessel diameter and reconstructed vascular volume, regardless of vessel type and branching order. BBB permeability was investigated with two different size of tracers. Stressed animals exhibited a greater BBB permeability to 40-kDa dextran, but not to 70-kDa dextran, which is suggestive of weakened vascular integrity following stress. Molecular analysis revealed significantly higher VEGFa mRNA expression and a reduction in claudin-5. In summary, chronic stress decreases the size of cerebral vessels and increases BBB permeability. These results may suggest that the sustained decrease in cerebro-vascular volume due to chronic stress leads to a hypoxic condition that causes molecular changes such as VEGF and claudin-5, which eventually impairs the function of BBB.
Highlights
Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system
The long-term effects of chronic stress on the cerebro-vascular volume and blood-brain barrier (BBB) permeability are investigated using longitudinal in vivo 2p dynamic imaging and we show that chronic restraint stress decreases the size of cerebral vessels and increases BBB permeability, accompanied with up-regulation of vascular endothelial growth factor (VEGF)
We investigated whether repeated restraint stress induced decreases in cerebro vascular volume and BBB permeability in mouse cortex with in vivo 2p imaging
Summary
Chronic stress disrupts brain homeostasis and adversely affects the cerebro-vascular system. The effects of chronic stress on cerebral vasculature and BBB permeability were studied using in vivo two-photon (2p) microscopic imaging with an injection of fluorescence-conjugated dextran. Chronic stress decreases the size of cerebral vessels and increases BBB permeability. These results may suggest that the sustained decrease in cerebro-vascular volume due to chronic stress leads to a hypoxic condition that causes molecular changes such as VEGF and claudin-5, which eventually impairs the function of BBB. Reduced cerebral blood volume (CBV) has been reported in chronically stressed rodents[12].
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