Antibodies to the α1-Adrenergic Receptor Cause Vascular Impairments in Rat Brain as Demonstrated by Magnetic Resonance Angiography 英文参考文献.docVIP

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Antibodies to the α1-Adrenergic Receptor Cause Vascular Impairments in Rat Brain as Demonstrated by Magnetic Resonance Angiography 英文参考文献.doc

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Antibodies to the α1-Adrenergic Receptor Cause Vascular Impairments in Rat Brain as Demonstrated by Magnetic Resonance Angiography 英文参考文献

Antibodiestothea1-AdrenergicReceptorCauseVascular ImpairmentsinRatBrainasDemonstratedbyMagnetic ResonanceAngiography PeterKarczewski1*,AndreasPohlmann2,BabetteWagenhaus2,NataliWisbrun3,PetraHempel1, BerndLemke4,RudolfKunze5,ThoralfNiendorf2,6,MarionBimmler7 1E.R.D.E.-AAK-Diagnostik GmbH, Berlin, Germany, 2Berlin Ultrahigh Field Facility (B.U.F.F.), Max Delbrueck Center for Molecular Medicine, Berlin, Germany, 3Animal Facilities,MaxDelbrueckCenterforMolecularMedicine,Berlin,Germany,4ITDepartment,MaxDelbrueckCenterforMolecularMedicine,Berlin,Germany,5E.R.D.E.e.V., Berlin, Germany, 6Experimental and Clinical Research Center, a joint cooperation between the Charite′ Medical Faculty and the Max Delbru¨ck Center for Molecular Medicine,Berlin,Germany,7AutoimmunityandGProtein-CoupledReceptors,MaxDelbrueckCenterforMolecularMedicine,Berlin,Germany Abstract Background: Circulating agonistic autoantibodies acting at G protein-coupled receptors have been associated with numerous sever pathologies in humans. Antibodies directed predominantly against the a1-adrenergig receptor were detectedinpatientssufferingfromwidespreaddiseasessuchashypertensionandtype2diabetes.Theirdeleteriousaction has been demonstrated for peripheral organs. We postulate that antibodies to the a1-adrenergig receptor are relevant pathomoleculesindiseasesofthecentralnervoussystemassociatedwithvascularimpairments. Methodology/Principal Findings: Using a rat model we studied the long-term action of antibodies against the a1- adrenergig receptor either induced by immunization with a receptor peptide or applied by intravenous injection. The vasculature in the rat brains was investigated by time-of-flight magnetic resonance angiography using a 9.4 Tesla small animalMRimagingsystem.Visualexaminationofmaximum-intensity-projections(MIPs)ofbrainangiographsrevealedthe development of vascular defects in antibody- exposed animals between three and eight months of treatment. Relative vascular areas were derived from repr