title: Sleep restriction impairs blood-brain barrier function.
abstract: The blood-brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose that changes of the BBB contribute to many pathophysiological processes in the brain of subjects with chronic sleep restriction (CSR). To achieve CSR that mimics a common pattern of human sleep loss, we quantified a new procedure of sleep disruption in mice by a week of consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelial and inducible nitric oxide synthase, endothelin1, and glucose transporter expression in cerebral microvessels of the BBB, but it also decreased 2-deoxy-glucose uptake by the brain. The expression of several tight junction proteins also was decreased, whereas the level of cyclooxygenase-2 increased. This coincided with an increase of paracellular permeability of the BBB to the small tracers sodium fluorescein and biotin. CSR for 6 d was sufficient to impair BBB structure and function, although the increase of paracellular permeability returned to baseline after 24 h of recovery sleep. This merits attention not only in neuroscience research but also in public health policy and clinical practice.
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
authors.forename: Junyun
authors.identifier: http://orcid.org/0000-0003-4325-5655
authors.initials: J
authors.lastname: He
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
authors.forename: Hung
authors.initials: H
authors.lastname: Hsuchou
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
authors.forename: Yi
authors.initials: Y
authors.lastname: He
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
authors.forename: Abba J
authors.initials: AJ
authors.lastname: Kastin
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808.
authors.forename: Yuping
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Blood-Brain Barrier Group, Pennington Biomedical Research Center, Baton Rouge, Louisiana 70808 biopotentialsllc@gmail.com.
authors.forename: Weihong
authors.initials: W
authors.lastname: Pan
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000378:metabolism / Q000503:physiopathology*; D001921:Brain / Q000378:metabolism / Q000503:physiopathology*; D015536:Down-Regulation; D042783:Endothelial Cells / Q000378:metabolism; D051272:Glucose Transporter Type 1 / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000378:metabolism; D010539:Permeability; D012890:Sleep / Q000502:physiology*; D012892:Sleep Deprivation / Q000378:metabolism / Q000503:physiopathology*
chemical_list: D051272:Glucose Transporter Type 1
keywords: BBB; glucose metabolism; sleep duration; sleep restriction; transport