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.
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.
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.
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.