SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury

WD Hill, DC Hess, A Martin-Studdard… - … of Neuropathology & …, 2004 - academic.oup.com
WD Hill, DC Hess, A Martin-Studdard, JJ Carothers, J Zheng, D Hale, M Maeda, SC Fagan…
Journal of Neuropathology & Experimental Neurology, 2004academic.oup.com
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 …
Abstract
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.
Oxford University Press