SDF-1 (CXCL12) Is Upregulated in the Ischemic Penumbra Following Stroke

Association with Bone Marrow Cell Homing to Injury

William D Hill, David C Hess, Angeline Martin-Studdard, Jo J. Carothers, Jianqing Zheng, David Hale, Manabu Maeda, Susan C. Fagan, James Edwin Carroll, Simon J. Conway

Research output: Contribution to journalArticle

300 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)84-96
Number of pages13
JournalJournal of neuropathology and experimental neurology
Volume63
Issue number1
DOIs
StatePublished - Jan 1 2004

Fingerprint

Bone Marrow Cells
Green Fluorescent Proteins
Stroke
Wounds and Injuries
Middle Cerebral Artery Infarction
Sutures
Bone Marrow
CXCR4 Receptors
Pericytes
Neuropil
Microglia
Chemokines
Astrocytes
Blood Vessels
Monocytes
Stem Cells
Transplants
Brain

Keywords

  • Astrocytes
  • Chemokine
  • Chemotactic
  • Ischemia
  • Microglia
  • Stem cells
  • Stromal-derived factor-1

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Neurology
  • Clinical Neurology
  • Cellular and Molecular Neuroscience

Cite this

SDF-1 (CXCL12) Is Upregulated in the Ischemic Penumbra Following Stroke : Association with Bone Marrow Cell Homing to Injury. / Hill, William D; Hess, David C; Martin-Studdard, Angeline; Carothers, Jo J.; Zheng, Jianqing; Hale, David; Maeda, Manabu; Fagan, Susan C.; Carroll, James Edwin; Conway, Simon J.

In: Journal of neuropathology and experimental neurology, Vol. 63, No. 1, 01.01.2004, p. 84-96.

Research output: Contribution to journalArticle

Hill, William D ; Hess, David C ; Martin-Studdard, Angeline ; Carothers, Jo J. ; Zheng, Jianqing ; Hale, David ; Maeda, Manabu ; Fagan, Susan C. ; Carroll, James Edwin ; Conway, Simon J. / SDF-1 (CXCL12) Is Upregulated in the Ischemic Penumbra Following Stroke : Association with Bone Marrow Cell Homing to Injury. In: Journal of neuropathology and experimental neurology. 2004 ; Vol. 63, No. 1. pp. 84-96.
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