Cited by 150Barrier Structure and Function StudiesAcute Ischemic Stroke ManagementNeuroinflammation and Neurodegeneration Mechanisms

Increased Blood–Brain Barrier Permeability and Brain Edema After Focal Cerebral Ischemia Induced by Hyperlipidemia: Role of Lipid Peroxidation and Calpain-1/2, Matrix Metalloproteinase-2/9, and RhoA Overactivation

ElAli, Ayman, Doeppner, Thorsten R., Zechariah, Anil, Hermann, Dirk M.·2011·Stroke

Abstract

Background and Purpose—: Hyperlipidemia is a highly prevalent risk factor for ischemic stroke. Its impact on brain injury and blood–brain barrier permeability, so far, has not been assessed in animal models of ischemic stroke. Methods—: Wild-type and apolipoprotein E −/− mice, fed with normal or cholesterol-rich high-fat food, were subjected to 30 minutes of middle cerebral artery occlusion. Ischemic injury, brain edema, IgG extravasation, lipid peroxidation, calpain-1/2, matrix metalloproteinase-2/9, and RhoA activation, and occludin expression were evaluated 24 hours after reperfusion. Results—: Cholesterol-rich food, but not apolipoprotein E deficiency, increased IgG extravasation and brain edema without influencing infarct area and the density of DNA fragmented cells. Increased lipid peroxidation and low-density lipoprotein oxidation were noticed in the brain of hyperlipidemic mice and were associated with increased activation of calpain-1/2 and matrix metalloproteinase-2/9, overactivation of RhoA and its guanine exchange factor leukemia-associated guanine exchange factor , and downregulation of the tight junction protein occludin in cerebral microvessels. Conclusions—: That postischemic blood–brain barrier permeability and brain edema are increased during hyperlipidemia points toward the importance of the recognition and adequate treatment of this highly prevalent condition. Translational studies should more adequately mimic risk factors prevalent in human stroke.

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Crossref · 10.1161/strokeaha.111.615559

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Authors
ElAli, A., Doeppner, T. R., Zechariah, A., & Hermann, D. M.
Affiliations
Essen University Hospital (DE)
Venue
Stroke
Published
2011-11
Volume
42
Issue
11
Pages
3238-3244
ISSN
  • 0039-2499 (ISSN-L)
  • 1524-4628
OpenAlex
W2104832976
Cited by
150
References
26
Citations by year
2026: 6 · 2025: 12 · 2024: 11 · 2023: 7 · 2022: 14 · 2021: 7 · 2020: 12 · 2019: 10 · 2018: 6 · 2017: 11 · 2016: 17 · 2015: 5 · 2014: 10 · 2013: 12 · 2012: 9
FWCI
5.65
Type
journal article
Language
en
Open access
closed
Locations
  • Stroke (publishedVersion)
  • PubMed (publishedVersion)
  • Universitätsbibliographie, Universität Duisburg-Essen (submittedVersion)
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Epidemiology › Acute Ischemic Stroke Management
  • Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Keywords
hyperlipidemia, blood-brain barrier permeability, cerebral edema, focal cerebral ischemia, ischemic stroke, middle cerebral artery occlusion, apolipoprotein E deficiency, high-cholesterol diet, IgG extravasation, lipid peroxidation, LDL oxidation, MMP2/9, RhoA, occludin, tight junctions, ischemia-reperfusion injury
MeSH terms
Animals, Blood-Brain Barrier, Brain Edema, Calpain, Capillary Permeability, Brain Ischemia, Enzyme Activation, Hyperlipidemias, Male, Mice, Inbred C57BL, Lipid Peroxidation, Mice, Knockout, rho GTP-Binding Proteins, rhoA GTP-Binding Protein, Matrix Metalloproteinase 2, Matrix Metalloproteinase 9, Mice

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