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

314 Scopus citations

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 2004

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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

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