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

Journal of Neuroinflammation

Tarja Malm¹  Jari Koistinaho³  Patrick M Sullivan²  Anna-Kaisa Ruotsalainen¹  Kaisa Savolainen¹  Sara Wojciechowski¹  Ekaterina Savchenko¹  Taisia Rolova¹  Hiramani Dhungana¹ 

[1] Department of Neurobiology, A. I. Virtanen Institute for Molecular Sciences, Biocenter Kuopio, University of Eastern Finland, P.O. Box 1627, FI-70211 Kuopio, Finland;Duke University and Geriatric Research Education Clinical Centre, DVAMC, Durham NC 27710, USA;Department of Oncology, Kuopio University Hospital, P.O. Box 1627, FI-70211 Kuopio, Finland

关键词: Aging;    Western diet;    Atherosclerosis;    Apolipoprotein E;    Inflammation;    Brain ischemia;   

Others  :  1152306
DOI  :  10.1186/1742-2094-10-102

 received in 2013-06-21, accepted in 2013-08-08,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Dhungana et al.; licensee BioMed Central Ltd.

【 图 表 】

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