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Hypercholesterolemia induced cerebral small vessel disease.

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  • 1Department of Neurology, University Hospital Würzburg, Würzburg, Germany.

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|August 11, 2017
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Hypercholesterolemia is linked to thrombotic cerebral small vessel disease (CSVD) in mice. This study highlights the Ldlr-/- mouse as a model for investigating CSVD, distinct from hypertension-related forms.

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Area of Science:

  • Neurology
  • Cardiovascular Research
  • Genetics

Background:

  • Hypercholesterolemia is a known risk factor for large vessel ischemic stroke.
  • The specific role of hypercholesterolemia in cerebral small vessel disease (CSVD) requires further elucidation.

Purpose of the Study:

  • To investigate the detailed relationship between hypercholesterolemia and CSVD.
  • To assess the utility of the Ldlr-/- mouse model for studying CSVD.

Main Methods:

  • Utilized Ldlr-/- and wild-type (WT) mice at 6 and 12 months of age.
  • Administered a high-fat diet to induce hypercholesterolemia in Ldlr-/- mice.
  • Analyzed cerebral microvasculature for erythrocyte stases, thrombotic occlusions, blood-brain barrier (BBB) dysfunction, and microbleeds.

Main Results:

  • Ldlr-/- mice showed increased erythrocyte stases at 6 months.
  • Significant thrombotic occlusions were observed in 12-month-old Ldlr-/- mice, unlike WT mice.
  • No significant gray matter BBB breakdown was noted in Ldlr-/- mice; microhemorrhages were rare.

Conclusions:

  • Hypercholesterolemia is associated with a thrombotic CSVD phenotype in Ldlr-/- mice.
  • This thrombotic CSVD phenotype differs from the hemorrhagic phenotype linked to hypertension.
  • Ldlr-/- mice serve as a suitable model for CSVD research.