Journal
JOURNAL OF NEUROPATHOLOGY AND EXPERIMENTAL NEUROLOGY
Volume 63, Issue 1, Pages 84-96Publisher
AMER ASSN NEUROPATHOLOGISTS INC
DOI: 10.1093/jnen/63.1.84
Keywords
astrocytes; chemokine; chemotactic; ischemia; microglia; stem cells; stromal-derived factor-1
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Funding
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [P01HL052813, R01HL060104, R01HL060714] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF NEUROLOGICAL DISORDERS AND STROKE [R01NS038540, R21NS043487, R21NS043439] Funding Source: NIH RePORTER
- NHLBI NIH HHS [HL60104, HL60714, HL52813] Funding Source: Medline
- NINDS NIH HHS [NS38540, NS43439, NS43487] Funding Source: Medline
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The chemokine stromal-derived factor-1 (SDF-1, also known as CXCL12) and its receptor CXCR4 have been implicated in homing of stem cells to the bone marrow and the homing of bone marrow-derived cells to sites of injury. Bone marrow cells infiltrate brain and give rise to long-term resident cells following injury. Therefore, SDF-1 and CXCR4 expression patterns in 40 mice were examined relative to the homing of bone marrow-derived cells to sites of ischemic injury using a stroke model. Mice received bone marrow transplants from green fluorescent protein (GFP) transgenic donors and later underwent a temporary middle cerebral artery suture occlusion (MCAo). SDF-1 was associated with blood vessels and cellular profiles by 24 hours through at least 30 days post-MCAo. SDF-1 expression was principally localized to the ischemic penumbra. The majority of SDF-1 expression was associated with reactive astrocytes; much of this was perivascular. GFP+ cells were associated with SDF-1-positive vessels and were also found in the neuropil of regions with increased SDF-1 immunoreactivity. Most vessel-associated GFP+ cells resemble pericytes or perivascular microglia and the majority of the GFP+ cells in the parenchyma displayed characteristics of activated microglial cells. These findings suggest SDF-1 is important in the homing of bone marrow-derived cells, especially monocytes, to areas of ischemic injury.
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