Journal Article

DZNE-2020-05764

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Hypercholesterolemia induced cerebral small vessel disease.

Kraft, P. (Corresponding author) ; Schuhmann, M. K. ; Garz, C.DZNE* ; Jandke, S.DZNE* ; Urlaub, D. ; Mencl, S. ; Zernecke, A. ; Heinze, H.-J.DZNE* ; Carare, R. O. ; Kleinschnitz, C. ; Schreiber, S. (Last author)DZNE*

2017
PLOS San Francisco, California, US

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Please use a persistent id in citations: doi:10.1371/journal.pone.0182822

Abstract: 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.

Keyword(s): Animals (MeSH) ; Blood-Brain Barrier: physiopathology (MeSH) ; Brain: physiopathology (MeSH) ; Cerebral Small Vessel Diseases: blood (MeSH) ; Cerebral Small Vessel Diseases: etiology (MeSH) ; Cerebral Small Vessel Diseases: genetics (MeSH) ; Cerebral Small Vessel Diseases: physiopathology (MeSH) ; Cholesterol: blood (MeSH) ; Diet, High-Fat (MeSH) ; Disease Models, Animal (MeSH) ; Hypercholesterolemia: blood (MeSH) ; Hypercholesterolemia: complications (MeSH) ; Hypercholesterolemia: genetics (MeSH) ; Hypercholesterolemia: physiopathology (MeSH) ; Male (MeSH) ; Mice (MeSH) ; Mice, Knockout (MeSH) ; Receptors, LDL: genetics (MeSH) ; Receptors, LDL ; Cholesterol

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Contributing Institute(s):

1. Pathophysiology of Dementia (AG Reymann)
2. U Clinical Researchers - Magdeburg (U Clinical Researchers - Magdeburg)

Research Program(s):

1. 342 - Disease Mechanisms and Model Systems (POF3-342) (POF3-342)
2. 344 - Clinical and Health Care Research (POF3-344) (POF3-344)

Appears in the scientific report 2017

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Database coverage:
; ; ; ; BIOSIS Previews ; Clarivate Analytics Master Journal List ; DOAJ Seal ; Ebsco Academic Search ; IF < 5 ; JCR ; SCOPUS ; Web of Science Core Collection ; Zoological Record

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