RT Journal Article
SR Electronic
T1 CD36/Fatty Acid Translocase, An Inflammatory Mediator, Is Involved in Hyperlipidemia-Induced Exacerbation in Ischemic Brain Injury
JF The Journal of Neuroscience
JO J. Neurosci.
FD Society for Neuroscience
SP 4661
OP 4670
DO 10.1523/JNEUROSCI.0982-08.2008
VO 28
IS 18
A1 Eunhee Kim
A1 Aaron T. Tolhurst
A1 Lu Ye Qin
A1 Xin-Yuan Chen
A1 Maria Febbraio
A1 Sunghee Cho
YR 2008
UL http://www.jneurosci.org/content/28/18/4661.abstract
AB 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.