SDF-1 (CXCL12) is upregulated in the ischemic penumbra following stroke: association with bone marrow cell homing to injury.
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.
Hill
William D
WD
Department of Cellular Biology and Anatomy, Medical College of Georgia, Augusta, Georgia 30912-2000, USA. whill@mail.mcg.edu
Hess
David C
DC
Martin-Studdard
Angeline
A
Carothers
Jo J
JJ
Zheng
Jianqing
J
Hale
David
D
Maeda
Manabu
M
Fagan
Susan C
SC
Carroll
James E
JE
Conway
Simon J
SJ
D000818:Animals; D001253:Astrocytes / Q000378:metabolism; D016026:Bone Marrow Transplantation; D001921:Brain / Q000098:blood supply / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000378:metabolism / Q000473:pathology*; D002465:Cell Movement / Q000502:physiology*; D002560:Cerebrovascular Circulation / Q000502:physiology; D054377:Chemokine CXCL12; D019743:Chemokines, CXC / Q000096:biosynthesis*; D004195:Disease Models, Animal; D005260:Female; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D020244:Infarction, Middle Cerebral Artery / Q000150:complications / Q000378:metabolism / Q000473:pathology; D008164:Luminescent Proteins / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism; D018613:Microscopy, Confocal; D019718:Receptors, CXCR4 / Q000378:metabolism; D015854:Up-Regulation
D054377:Chemokine CXCL12; D019743:Chemokines, CXC; C515256:Cxcl12 protein, mouse; D008164:Luminescent Proteins; D019718:Receptors, CXCR4; D049452:Green Fluorescent Proteins