Abstract
Stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptors CXCR4 and CXCR7 play important roles in brain repair after ischemic stroke, as SDF-1/ CXCR4/CXCR7 chemokine signaling is critical for recruiting stem cells to sites of ischemic injury. Upregulation of SDF-1/CXCR4/CXCR7 chemokine signaling in the ischemic regions has been well-documented in the animal models of ischemic stroke, but not in human ischemic brain. Here, we found that protein expression of SDF-1 and CXCR7, but not CXCR4, were significantly increased in the cortical peri-infarct regions (penumbra) after ischemic stroke in human, compared with adjacent normal tissues and control subjects. Double-label fluorescence immunohistochemistry shows that SDF-1 and CXCR4 proteins were expressed in neuronal cells and astrocytes in the normal brain tissue and peri-infarct regions. CXCR7 protein was also observed in neuronal cells and astrocytes in the normal cortical regions, but predominantly in astrocytes in the penumbra of ischemic brain. Our data suggest that ischemic stroke in human leads to an increase in the expression of SDF-1 and CXCR7, but not CXCR4, in the peri-infarct cerebral cortex. Our findings suggest that chemokine SFD-1 is expressed not only in animal models of stroke, but also in the human brain after an ischemic injury. In addition, unlike animals, CXCR7 may be the primary receptor of SDF-1 in human stroke brain.
Highlights
Stromal cell-derived factor 1 (SDF-1), known as CX-C motif chemokine 12 (CXCL12), is a chemokine protein that ubiquitously expressed in many tissues and all cell types in the central nervous system (CNS)[1]
The major finding of this study is that ischemic stroke in human leads to an increase in the expression of SDF-1 and CXCR7, but not CXCR4, in the peri-infarct cerebral cortex compared with the adjacent normal brain and ischemic core
The mechanism underlying stem cell homing to ischemic regions is unclear, the overexpression and secretion of SDF-1 by ischemic tissues could develop a gradient in circulation and guides CXCR4-postive stem cell recruitment from bone marrow and neurogenic niches in the brain to the injured site [24]
Summary
Stromal cell-derived factor 1 (SDF-1), known as CX-C motif chemokine 12 (CXCL12), is a chemokine protein that ubiquitously expressed in many tissues and all cell types in the central nervous system (CNS)[1]. SDF-1 signaling is initiated by ligation of the chemokine with its G-protein-coupled receptor C-X-C chemokine receptor type 4 (CXCR-4; known as fusin or CD184) [2] that is expressed in neurons, microglia, astrocytes, bone marrow stromal cells (BMSCs), and some other stem cells [3]. A recent study shows that SDF-1 level is increased in the serum of patients with stroke and the serum SDF-1 change is positively correlated with infarct volume and severity of stroke in patients [18,19,20] Taken together, these findings suggest that SDF-1/CXCR4/CXCR7 signaling axis plays an important role in neurogenesis and angiogenesis after ischemic stroke. Our data suggest that SDF-1 play a role in brain repair after ischemic stroke in human through a CXCR7 dependent mechanism
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