SleepRestrictionImpairsBlood-BrainBarrierFunction XJunyunHe,HungHsuchou,YiHe,AbbaJ.Kastin,YupingWang,andWeihongPan Blood-BrainBarrierGroup,PenningtonBiomedicalResearchCenter,BatonRouge,Louisiana70808

The blood‐brain barrier (BBB) is a large regulatory and exchange interface between the brain and peripheral circulation. We propose thatchangesoftheBBBcontributetomanypathophysiologicalprocessesinthebrainofsubjectswithchronicsleeprestriction(CSR).To achieveCSRthatmimicsacommonpatternofhumansleeploss,wequantifiedanewprocedureofsleepdisruptioninmicebyaweekof consecutive sleep recording. We then tested the hypothesis that CSR compromises microvascular function. CSR not only diminished endothelialandinduciblenitricoxidesynthase,endothelin1,andglucosetransporterexpressionincerebralmicrovesselsoftheBBB,but italsodecreased2-deoxy-glucoseuptakebythebrain.Theexpressionofseveraltightjunctionproteinsalsowasdecreased,whereasthe levelofcyclooxygenase-2increased.ThiscoincidedwithanincreaseofparacellularpermeabilityoftheBBBtothesmalltracerssodium fluoresceinandbiotin.CSRfor6dwassufficienttoimpairBBBstructureandfunction,althoughtheincreaseofparacellularpermeability returnedtobaselineafter24hofrecoverysleep.Thismeritsattentionnotonlyinneuroscienceresearchbutalsoinpublichealthpolicy andclinicalpractice.