Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder英文文献资料.docVIP

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Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder英文文献资料.doc

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Breaching the Blood-Brain Barrier as a Gate to Psychiatric Disorder英文文献资料

HindawiPublishingCorporation CardiovascularPsychiatryandNeurology Volume2009,ArticleID278531,7pages doi:10.1155/2009/278531 Hypothesis BreachingtheBlood-BrainBarrierasaGateto PsychiatricDisorder HadarShalev, YonatanSerlin, andAlonFriedman 1 2 2 1 DepartmentofPsychiatry,SorokaUniversityMedicalCenter;ZlotowskiCenterforNeuroscience, Ben-GurionUniversityoftheNegev,Beer-Sheva84105,Israel 2 DepartmentofPhysiologyandNeurosurgery,SorokaUniversityMedicalCenter;ZlotowskiCenterforNeuroscience, Ben-GurionUniversityoftheNegev,Beer-Sheva84105,Israel CorrespondenceshouldbeaddressedtoAlonFriedman,alonf@bgu.ac.il Received2April2009;Accepted4July2009 RecommendedbyHariManev The mechanisms underlying the development and progression of psychiatric illnesses are only partially known. Clinical data suggest blood-brain barrier (BBB) breakdown and in?ammation are involved in some patients groups. Here we put forward the“BBBhypothesis”andabnormalblood-braincommunicationaskeymechanismsleadingtoneuronaldysfunctionunderlying disturbedcognition,mood,andbehavior.Basedonaccumulatingclinicaldataandanimalexperiments,weproposethatevents withinthe“neurovascularunit”areinitiatedbyafocalBBBbreakdown,andareassociatedwithdysfunctionofbrainastrocytes, a local in?ammatory response, pathological synaptic plasticity, and increased network connectivity. Our hypothesis should bevalidated inanimalmodelsofpsychiatric diseasesandBBBbreakdown. Recently developed imaging approaches openthe opportunity to challenge our hypothesis in patients. We propose that molecular mechanisms controlling BBB permeability, astrocyticfunctions,andin?ammationmaybecomenoveltargetsforthepreventionandtreatmentofpsychiatricdisorders. Copyright?2009HadarShalevetal.ThisisanopenaccessarticledistributedundertheCreativeCommonsAttributionLicense, whichpermitsunrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalworkisproperlycited. 1.StructureandFunctionof theBlood-BrainBarrier adis