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Open Access 01-12-2013 | Research

Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele

Authors: Hiramani Dhungana, Taisia Rolova, Ekaterina Savchenko, Sara Wojciechowski, Kaisa Savolainen, Anna-Kaisa Ruotsalainen, Patrick M Sullivan, Jari Koistinaho, Tarja Malm

Published in: Journal of Neuroinflammation | Issue 1/2013

Abstract

Background

Numerous clinical trials in stroke have failed, most probably partially due to preclinical studies using young, healthy male rodents with little relevance to the heterogenic conditions of human stroke. Co-morbid conditions such as atherosclerosis and infections coupled with advanced age are known to contribute to increased risk of cerebrovascular diseases. Clinical and preclinical studies have shown that the E4 allele of human apolipoprotein (ApoE4) is linked to poorer outcome in various conditions of brain injury and neurodegeneration, including cerebral ischemia. Since ApoE is a known regulator of lipid homeostasis, we studied the impact of a high-cholesterol diet in aged mice in the context of relevant human ApoE isoforms on the outcome of focal brain ischemia.

Methods

Aged mice expressing human E3 and E4 isoforms of ApoE in C57BL/6J background and C57BL/6J mice fed on either a high-fat diet or a normal diet underwent permanent middle cerebral artery occlusion. The impact of a high-cholesterol diet was assessed by measuring the serum cholesterol level and the infarction volume was determined by magnetic resonance imaging. Sensorimotor deficits were assessed using an adhesive removal test and the findings were correlated with inflammatory markers.

Results

We show that expression of human ApoE4 renders aged mice fed with a western-type diet more susceptible to sensorimotor deficits upon stroke. These deficits are not associated with atherosclerosis but are accompanied with altered astroglial activation, neurogenesis, cyclooxygenase-2 immunoreactivity and increased plasma IL-6.

Conclusions

Our results support the hypothesis that ApoE alleles modify the inflammatory responses in the brain and the periphery, thus contributing to altered functional outcome following stroke.

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Title: Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele
Authors: Hiramani Dhungana
Taisia Rolova
Ekaterina Savchenko
Sara Wojciechowski
Kaisa Savolainen
Anna-Kaisa Ruotsalainen
Patrick M Sullivan
Jari Koistinaho
Tarja Malm
Publication date: 01-12-2013
Publisher: BioMed Central
Published in: Journal of Neuroinflammation / Issue 1/2013
Electronic ISSN: 1742-2094
DOI: https://doi.org/10.1186/1742-2094-10-102

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Western-type diet modulates inflammatory responses and impairs functional outcome following permanent middle cerebral artery occlusion in aged mice expressing the human apolipoprotein E4 allele

Abstract

Background

Methods

Results

Conclusions

Keynote webinar | Spotlight on medication adherence

Springer Medicine

Abstract

Background

Methods

Results

Conclusions

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