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

J Neuropathol Exp Neurol. 2004 Jan;63(1):84-96. doi: 10.1093/jnen/63.1.84.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Astrocytes / metabolism
  • Bone Marrow Transplantation*
  • Brain / blood supply
  • Brain / metabolism
  • Brain / pathology
  • Brain Ischemia / etiology
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Cell Movement / physiology*
  • Cerebrovascular Circulation / physiology
  • Chemokine CXCL12
  • Chemokines, CXC / biosynthesis*
  • Disease Models, Animal
  • Female
  • Green Fluorescent Proteins
  • Immunohistochemistry
  • In Situ Hybridization
  • Infarction, Middle Cerebral Artery / complications
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / pathology
  • Luminescent Proteins / genetics
  • Male
  • Mice
  • Mice, Transgenic
  • Microglia / metabolism
  • Microscopy, Confocal
  • Receptors, CXCR4 / metabolism
  • Up-Regulation

Substances

  • Chemokine CXCL12
  • Chemokines, CXC
  • Cxcl12 protein, mouse
  • Luminescent Proteins
  • Receptors, CXCR4
  • Green Fluorescent Proteins