Exposure to Lipopolysaccharide andor Unconjugated Bilirubin Impair the Integrity and Function of Brain Microvascular Endothelial Cells 英文参考文献.docVIP

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Exposure to Lipopolysaccharide andor Unconjugated Bilirubin Impair the Integrity and Function of Brain Microvascular Endothelial Cells 英文参考文献.doc

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Exposure to Lipopolysaccharide andor Unconjugated Bilirubin Impair the Integrity and Function of Brain Microvascular Endothelial Cells 英文参考文献

ExposuretoLipopolysaccharideand/orUnconjugated BilirubinImpairtheIntegrityandFunctionofBrain MicrovascularEndothelialCells FilipaL.Cardoso1,Agnes′ Kittel2,SzilviaVeszelka3,Ine?sPalmela1,AndreaTo′th3,DoraBrites1,4, Ma′riaA.Deli3,MariaA.Brito1,4* 1Research Institute for Medicines and Pharmaceutical Sciences, Faculty of Pharmacy, University of Lisbon, Lisbon, Portugal, 2Institute of Experimental Medicine, HungarianAcademyofSciences,Budapest,Hungary,3LaboratoryofMolecularNeurobiology,InstituteofBiophysics,BiologicalResearchCentre,HungarianAcademyof Sciences,Szeged,Hungary,4DepartmentofBiochemistryandHumanBiology,FacultyofPharmacy,UniversityofLisbon,Lisbon,Portugal Abstract Background: Sepsis and jaundice are common conditions in newborns that can lead to brain damage. Though lipopolysaccharide (LPS) is known to alter the integrity of the blood-brain barrier (BBB), little is known on the effects of unconjugated bilirubin (UCB) andeven less on the joint effects of UCB and LPS on brain microvascular endothelial cells (BMEC). Methodology/PrincipalFindings:MonolayersofprimaryratBMECweretreatedwith1mg/mlLPSand/or50mMUCB,inthe presenceof100mMhumanserumalbumin,for4or24h.Co-culturesofBMECwithastroglialcells,amorecomplexBBB model, were used in selected experiments. LPS led to apoptosis and UCB induced both apoptotic and necrotic-like cell death. LPS and UCB led to inhibition of P-glycoprotein and activation of matrix metalloproteinases-2 and -9 in mono- cultures. Transmission electron microscopy evidenced apoptotic bodies, as well as damaged mitochondria and rough endoplasmic reticulum in BMEC by either insult. Shorter cell contacts and increased caveolae-like invaginations were noticeableinLPS-treatedcellsandlossofintercellularjunctionswasobservedupontreatmentwithUCB.Bothcompounds triggeredimpairmentofendothelialpermeabilityandtransendothelialelectricalresistancebothinmono-andco-cultures. The functional changes were confirmed by alterations in immunostaining for junctiona