Migration of enhanced green fluorescent protein expressing bone marrow-derived microglia/macrophage into the mouse brain following permanent focal ischemia.
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.
Tanaka
R
R
Department of Neurology, Juntendo University School of Medicine, 2-1-1, Hongo, Bunkyo-ku, Tokyo 113-8421, Japan.
Komine-Kobayashi
M
M
Mochizuki
H
H
Yamada
M
M
Furuya
T
T
Migita
M
M
Shimada
T
T
Mizuno
Y
Y
Urabe
T
T
D000818:Animals; D001853:Bone Marrow / Q000473:pathology* / Q000528:radiation effects; D002545:Brain Ischemia / Q000378:metabolism / Q000473:pathology*; D002135:Calcium-Binding Proteins / Q000378:metabolism / Q000528:radiation effects; D002452:Cell Count; D002465:Cell Movement / Q000528:radiation effects; D002490:Central Nervous System / Q000293:injuries / Q000503:physiopathology / Q000528:radiation effects; D002678:Chimera / Q000378:metabolism; D004307:Dose-Response Relationship, Radiation; D005472:Fluorouracil / Q000633:toxicity; D049452:Green Fluorescent Proteins; D007150:Immunohistochemistry / Q000379:methods; D007166:Immunosuppressive Agents; D020244:Infarction, Middle Cerebral Artery / Q000378:metabolism / Q000503:physiopathology; D008164:Luminescent Proteins / Q000378:metabolism; D008264:Macrophages / Q000473:pathology / Q000528:radiation effects; D051379:Mice; D008822:Mice, Transgenic; D008840:Microfilament Proteins; D017628:Microglia / Q000473:pathology* / Q000528:radiation effects; D008869:Microtubule-Associated Proteins / Q000378:metabolism / Q000528:radiation effects; D013997:Time Factors; D019737:Transplants; D014916:Whole-Body Irradiation
C491049:Aif1 protein, mouse; D002135:Calcium-Binding Proteins; D007166:Immunosuppressive Agents; D008164:Luminescent Proteins; D008840:Microfilament Proteins; D008869:Microtubule-Associated Proteins; D049452:Green Fluorescent Proteins; D005472:Fluorouracil