QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 30, 2008, 28(18):4661-4670; doi:10.1523/JNEUROSCI.0982-08.2008

This Article Full Text Full Text (PDF) Supplemental Data Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Google Scholar Articles by Kim, E. Articles by Cho, S. PubMed PubMed Citation Articles by Kim, E. Articles by Cho, S.

 Previous Article  |  Next Article 

Neurobiology of Disease
CD36/Fatty Acid Translocase, An Inflammatory Mediator, Is Involved in Hyperlipidemia-Induced Exacerbation in Ischemic Brain Injury

Eunhee Kim,¹ Aaron T. Tolhurst,¹ Lu Ye Qin,¹ Xin-Yuan Chen,¹ Maria Febbraio,² and Sunghee Cho^1,3

¹Burke Medical Research Institute, White Plains, New York 10605, ²Department of Cell Biology, Cleveland Clinic, Cleveland, Ohio 44195, and ³Department of Neurology/Neuroscience, Weill Medical College of Cornell University, New York, New York 10021

Correspondence should be addressed to Dr. Sunghee Cho, Department of Neuroscience, Weill Cornell Medical College at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605. Email: suc2002{at}med.cornell.edu

Hyperlipidemia with accompanying increase in peripheral inflammation is a risk factor for stroke. The effect of excess lipids on stroke-induced injury and the mechanism by which lipid-mediated inflammatory responses contribute to stroke are not known. We investigated these uncertainties by subjecting normal and hyperlipidemic mice to transient middle cerebral artery occlusion, followed by measurement of stroke severity and inflammatory response. Infarct size, swelling, and lipid contents were significantly increased in the high-fat fed ApoE knock-out mice, as was the expression of the inflammatory mediators CD36 and monocyte chemoattractant protein 1 (MCP-1) in the brain and periphery. Furthermore, the hyperlipidemic mice exhibited numerous foam cells, a probable cause of increased swelling and postischemic inflammation, in the peri-infarct area. Genetic deletion of cd36 in the hyperlipidemic condition reduced proinflammatory chemokine/receptor and cytokines (MCP-1, CC chemokine receptor 2, and interleukins 1β and 6), in the brain 6 h after ischemia. The reduced proinflammatory response also resulted in smaller ischemic injury, less swelling, and fewer foam cells at 3 d after ischemia. The results show that hyperlipidemia-induced inflammation is a negative factor for stroke outcomes and indicate that downregulating CD36 may be an effective therapeutic strategy for reducing the impact of stroke in hyperlipidemic subjects.

Key words: CD36; foam cell formation; inflammation; ischemia; macrophage; stroke

---

Received Jan. 11, 2008; revised March 21, 2008; accepted March 22, 2008.

Correspondence should be addressed to Dr. Sunghee Cho, Department of Neuroscience, Weill Cornell Medical College at Burke Medical Research Institute, 785 Mamaroneck Avenue, White Plains, NY 10605. Email: suc2002{at}med.cornell.edu

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help