000139442 001__ 139442 000139442 005__ 20240321220623.0 000139442 0247_ $$2doi$$a10.1371/journal.pone.0182822 000139442 0247_ $$2pmid$$apmid:28796818 000139442 0247_ $$2pmc$$apmc:PMC5552130 000139442 0247_ $$2altmetric$$aaltmetric:23608117 000139442 037__ $$aDZNE-2020-05764 000139442 041__ $$aEnglish 000139442 082__ $$a610 000139442 1001_ $$0P:(DE-HGF)0$$aKraft, Peter$$b0$$eCorresponding author 000139442 245__ $$aHypercholesterolemia induced cerebral small vessel disease. 000139442 260__ $$aSan Francisco, California, US$$bPLOS$$c2017 000139442 264_1 $$2Crossref$$3online$$bPublic Library of Science (PLoS)$$c2017-08-10 000139442 3367_ $$2DRIVER$$aarticle 000139442 3367_ $$2DataCite$$aOutput Types/Journal article 000139442 3367_ $$0PUB:(DE-HGF)16$$2PUB:(DE-HGF)$$aJournal Article$$bjournal$$mjournal$$s1602767184_1198 000139442 3367_ $$2BibTeX$$aARTICLE 000139442 3367_ $$2ORCID$$aJOURNAL_ARTICLE 000139442 3367_ $$00$$2EndNote$$aJournal Article 000139442 520__ $$aBackgroundWhile hypercholesterolemia plays a causative role for the development of ischemic stroke in large vessels, its significance for cerebral small vessel disease (CSVD) remains unclear. We thus aimed to understand the detailed relationship between hypercholesterolemia and CSVD using the well described Ldlr-/- mouse model.MethodsWe used Ldlr-/- mice (n = 16) and wild-type (WT) mice (n = 15) at the age of 6 and 12 months. Ldlr-/- mice develop high plasma cholesterol levels following a high fat diet. We analyzed cerebral capillaries and arterioles for intravascular erythrocyte accumulations, thrombotic vessel occlusions, blood-brain barrier (BBB) dysfunction and microbleeds.ResultsWe found a significant increase in the number of erythrocyte stases in 6 months old Ldlr-/- mice compared to all other groups (P < 0.05). Ldlr-/- animals aged 12 months showed the highest number of thrombotic occlusions while in WT animals hardly any occlusions could be observed (P < 0.001). Compared to WT mice, Ldlr-/- mice did not display significant gray matter BBB breakdown. Microhemorrhages were observed in one Ldlr-/- mouse that was 6 months old. Results did not differ when considering subcortical and cortical regions.ConclusionsIn Ldlr-/- mice, hypercholesterolemia is related to a thrombotic CSVD phenotype, which is different from hypertension-related CSVD that associates with a hemorrhagic CSVD phenotype. Our data demonstrate a relationship between hypercholesterolemia and the development of CSVD. Ldlr-/- mice appear to be an adequate animal model for research into CSVD. 000139442 536__ $$0G:(DE-HGF)POF3-342$$a342 - Disease Mechanisms and Model Systems (POF3-342)$$cPOF3-342$$fPOF III$$x0 000139442 536__ $$0G:(DE-HGF)POF3-344$$a344 - Clinical and Health Care Research (POF3-344)$$cPOF3-344$$fPOF III$$x1 000139442 542__ $$2Crossref$$i2017-08-10$$uhttp://creativecommons.org/licenses/by/4.0/ 000139442 588__ $$aDataset connected to CrossRef, PubMed, 000139442 650_7 $$2NLM Chemicals$$aReceptors, LDL 000139442 650_7 $$097C5T2UQ7J$$2NLM Chemicals$$aCholesterol 000139442 650_2 $$2MeSH$$aAnimals 000139442 650_2 $$2MeSH$$aBlood-Brain Barrier: physiopathology 000139442 650_2 $$2MeSH$$aBrain: physiopathology 000139442 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: blood 000139442 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: etiology 000139442 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: genetics 000139442 650_2 $$2MeSH$$aCerebral Small Vessel Diseases: physiopathology 000139442 650_2 $$2MeSH$$aCholesterol: blood 000139442 650_2 $$2MeSH$$aDiet, High-Fat 000139442 650_2 $$2MeSH$$aDisease Models, Animal 000139442 650_2 $$2MeSH$$aHypercholesterolemia: blood 000139442 650_2 $$2MeSH$$aHypercholesterolemia: complications 000139442 650_2 $$2MeSH$$aHypercholesterolemia: genetics 000139442 650_2 $$2MeSH$$aHypercholesterolemia: physiopathology 000139442 650_2 $$2MeSH$$aMale 000139442 650_2 $$2MeSH$$aMice 000139442 650_2 $$2MeSH$$aMice, Knockout 000139442 650_2 $$2MeSH$$aReceptors, LDL: genetics 000139442 7001_ $$0P:(DE-HGF)0$$aSchuhmann, Michael K$$b1 000139442 7001_ $$0P:(DE-2719)2813207$$aGarz, Cornelia$$b2$$udzne 000139442 7001_ $$0P:(DE-2719)2813348$$aJandke, Solveig$$b3$$udzne 000139442 7001_ $$0P:(DE-HGF)0$$aUrlaub, Daniela$$b4 000139442 7001_ $$0P:(DE-HGF)0$$aMencl, Stine$$b5 000139442 7001_ $$0P:(DE-HGF)0$$aZernecke, Alma$$b6 000139442 7001_ $$0P:(DE-2719)2260426$$aHeinze, Hans-Jochen$$b7$$udzne 000139442 7001_ $$0P:(DE-HGF)0$$aCarare, Roxana O$$b8 000139442 7001_ 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