001     139442
005     20240321220623.0
024 7 _ |a 10.1371/journal.pone.0182822
|2 doi
024 7 _ |a pmid:28796818
|2 pmid
024 7 _ |a pmc:PMC5552130
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037 _ _ |a DZNE-2020-05764
041 _ _ |a English
082 _ _ |a 610
100 1 _ |a Kraft, Peter
|0 P:(DE-HGF)0
|b 0
|e Corresponding author
245 _ _ |a Hypercholesterolemia induced cerebral small vessel disease.
260 _ _ |a San Francisco, California, US
|c 2017
|b PLOS
264 _ 1 |3 online
|2 Crossref
|b Public Library of Science (PLoS)
|c 2017-08-10
336 7 _ |a article
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336 7 _ |a Output Types/Journal article
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336 7 _ |a Journal Article
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336 7 _ |a ARTICLE
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336 7 _ |a JOURNAL_ARTICLE
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336 7 _ |a Journal Article
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520 _ _ |a BackgroundWhile 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.
536 _ _ |a 342 - Disease Mechanisms and Model Systems (POF3-342)
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536 _ _ |a 344 - Clinical and Health Care Research (POF3-344)
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542 _ _ |i 2017-08-10
|2 Crossref
|u http://creativecommons.org/licenses/by/4.0/
588 _ _ |a Dataset connected to CrossRef, PubMed,
650 _ 7 |a Receptors, LDL
|2 NLM Chemicals
650 _ 7 |a Cholesterol
|0 97C5T2UQ7J
|2 NLM Chemicals
650 _ 2 |a Animals
|2 MeSH
650 _ 2 |a Blood-Brain Barrier: physiopathology
|2 MeSH
650 _ 2 |a Brain: physiopathology
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: blood
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: etiology
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: genetics
|2 MeSH
650 _ 2 |a Cerebral Small Vessel Diseases: physiopathology
|2 MeSH
650 _ 2 |a Cholesterol: blood
|2 MeSH
650 _ 2 |a Diet, High-Fat
|2 MeSH
650 _ 2 |a Disease Models, Animal
|2 MeSH
650 _ 2 |a Hypercholesterolemia: blood
|2 MeSH
650 _ 2 |a Hypercholesterolemia: complications
|2 MeSH
650 _ 2 |a Hypercholesterolemia: genetics
|2 MeSH
650 _ 2 |a Hypercholesterolemia: physiopathology
|2 MeSH
650 _ 2 |a Male
|2 MeSH
650 _ 2 |a Mice
|2 MeSH
650 _ 2 |a Mice, Knockout
|2 MeSH
650 _ 2 |a Receptors, LDL: genetics
|2 MeSH
700 1 _ |a Schuhmann, Michael K
|0 P:(DE-HGF)0
|b 1
700 1 _ |a Garz, Cornelia
|0 P:(DE-2719)2813207
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|u dzne
700 1 _ |a Jandke, Solveig
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700 1 _ |a Urlaub, Daniela
|0 P:(DE-HGF)0
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700 1 _ |a Mencl, Stine
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700 1 _ |a Zernecke, Alma
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700 1 _ |a Heinze, Hans-Jochen
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700 1 _ |a Carare, Roxana O
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700 1 _ |a Kleinschnitz, Christoph
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700 1 _ |a Schreiber, Stefanie
|0 P:(DE-2719)2812631
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773 1 8 |a 10.1371/journal.pone.0182822
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773 _ _ |a 10.1371/journal.pone.0182822
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910 1 _ |a Deutsches Zentrum für Neurodegenerative Erkrankungen
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Marc 21