Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia

Neuroscience. 2003;117(3):531-9. doi: 10.1016/s0306-4522(02)00954-5.


Brain ischemia induces a marked response of resident microglia and hematopoietic cells including monocytes/macrophages. The present study was designed to assess the distribution of microglia/macrophages in cerebral ischemia using bone marrow chimera mice known to express enhanced green fluorescent protein (EGFP). At 24 h after middle cerebral artery occlusion (MCAO), many round-shaped EGFP-positive cells migrated to the ischemic core and peri-infarct area. At 48-72 h after MCAO, irregular round- or oval-shaped EGFP/ionized calcium-binding adapter molecule 1 (Iba 1)-positive cells increased in the transition zone, while many amoeboid-shaped or large-cell-body EGFP/Iba 1-positive cells were increased in number in the innermost area of ischemia. At 7 days after MCAO, many process-bearing ramified shaped EGFP/Iba 1-positive cells were detected in the transition to the peri-infarct area, while phagocytic cells were distributed in the transition to the core area of the infarction. The distribution of these morphologically variable EGFP/Iba 1-positive cells was similar up to 14 days from MCAO. The present study directly showed the migration and distribution of bone marrow-derived monocytes/macrophages and the relationship between resident microglia and infiltrated hematogenous element in ischemic mouse brain. It is important to study the distribution of intrinsic and extrinsic microglia/macrophage in ischemic brain, since such findings may allow the design of appropriate gene-delivery system using exogenous microglia/macrophages to the ischemic brain area.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Bone Marrow / pathology*
  • Bone Marrow / radiation effects
  • Brain Ischemia / metabolism
  • Brain Ischemia / pathology*
  • Calcium-Binding Proteins / metabolism
  • Calcium-Binding Proteins / radiation effects
  • Cell Count
  • Cell Movement* / radiation effects
  • Central Nervous System / injuries
  • Central Nervous System / physiopathology
  • Central Nervous System / radiation effects
  • Chimera / metabolism
  • Dose-Response Relationship, Radiation
  • Fluorouracil / toxicity
  • Green Fluorescent Proteins
  • Immunohistochemistry / methods
  • Immunosuppressive Agents
  • Infarction, Middle Cerebral Artery / metabolism
  • Infarction, Middle Cerebral Artery / physiopathology
  • Luminescent Proteins / metabolism
  • Macrophages / pathology
  • Macrophages / radiation effects
  • Mice
  • Mice, Transgenic
  • Microfilament Proteins
  • Microglia / pathology*
  • Microglia / radiation effects
  • Microtubule-Associated Proteins / metabolism
  • Microtubule-Associated Proteins / radiation effects
  • Time Factors
  • Transplants
  • Whole-Body Irradiation


  • Aif1 protein, mouse
  • Calcium-Binding Proteins
  • Immunosuppressive Agents
  • Luminescent Proteins
  • Microfilament Proteins
  • Microtubule-Associated Proteins
  • Green Fluorescent Proteins
  • Fluorouracil