OBJECTIVE: Hyperlipidemia exacerbates ischemic stroke outcome and increases CD36 expression in the postischemic brain as well as in peripheral monocytes/macrophages. By exchanging bone marrow-derived cells between CD36-expressing and CD36-deficient mice, this study investigates the contribution of peripheral CD36 in comparison with that of brain CD36 to stroke pathology in hyperlipidemia. METHODS: Following bone marrow transplantation, mice were fed a high-fat diet for 11 weeks and then subjected to ischemic stroke. Stroke outcome, expression of brain CD36, monocyte chemoattractant protein-1 (MCP-1), CCR2, and plasma MCP-1 levels were determined at 3 days postischemia. CD36 and CCR2 expression were also determined in splenocytes incubated with serum obtained from CD36-expressing or CD36-deficient mice. RESULTS: Infiltrating immune cells from the periphery are the major source of CD36 in the postischemic brain and contribute to stroke-induced brain injury. This CD36 effect was dependent on the modulation of MCP-1 and CCR2 expression in peripheral immune cells as well as CD36-expressing cells in the host brain. INTERPRETATION: This study demonstrates that CD36 expressed in the periphery and brain synergize in ischemic brain injury through regulation of the MCP-1/CCR2 chemokine axis in hyperlipidemic conditions.
OBJECTIVE:Hyperlipidemia exacerbates ischemic stroke outcome and increases CD36 expression in the postischemic brain as well as in peripheral monocytes/macrophages. By exchanging bone marrow-derived cells between CD36-expressing and CD36-deficientmice, this study investigates the contribution of peripheral CD36 in comparison with that of brain CD36 to stroke pathology in hyperlipidemia. METHODS: Following bone marrow transplantation, mice were fed a high-fat diet for 11 weeks and then subjected to ischemic stroke. Stroke outcome, expression of brain CD36, monocyte chemoattractant protein-1 (MCP-1), CCR2, and plasma MCP-1 levels were determined at 3 days postischemia. CD36 and CCR2 expression were also determined in splenocytes incubated with serum obtained from CD36-expressing or CD36-deficientmice. RESULTS: Infiltrating immune cells from the periphery are the major source of CD36 in the postischemic brain and contribute to stroke-induced brain injury. This CD36 effect was dependent on the modulation of MCP-1 and CCR2 expression in peripheral immune cells as well as CD36-expressing cells in the host brain. INTERPRETATION: This study demonstrates that CD36 expressed in the periphery and brain synergize in ischemic brain injury through regulation of the MCP-1/CCR2 chemokine axis in hyperlipidemic conditions.
Authors: C M Coughlan; C M McManus; M Sharron; Z Gao; D Murphy; S Jaffer; W Choe; W Chen; J Hesselgesser; H Gaylord; A Kalyuzhny; V M Lee; B Wolf; R W Doms; D L Kolson Journal: Neuroscience Date: 2000 Impact factor: 3.590
Authors: M Febbraio; E A Podrez; J D Smith; D P Hajjar; S L Hazen; H F Hoff; K Sharma; R L Silverstein Journal: J Clin Invest Date: 2000-04 Impact factor: 14.808
Authors: A Flügel; G Hager; A Horvat; C Spitzer; G M Singer; M B Graeber; G W Kreutzberg; F W Schwaiger Journal: J Cereb Blood Flow Metab Date: 2001-01 Impact factor: 6.200
Authors: Theo Diamandis; Chiara Gonzales-Portillo; Gabriel S Gonzales-Portillo; Meaghan Staples; Mia C Borlongan; Diana Hernandez; Sandra Acosta; Cesar V Borlongan Journal: Med Hypotheses Date: 2013-08-30 Impact factor: 1.538