Iba1(+)/NG2(+) macrophage-like cells expressing a variety of neuroprotective factors ameliorate ischemic damage of the brain.
In a transient 90-min middle cerebral artery occlusion (MCAO) model of rats, a large ischemic lesion is formed where macrophage-like cells massively accumulate, many of which express a macrophage marker, Iba1, and an oligodendrocyte progenitor cell marker, NG2 chondroitin sulfate proteoglycan (NG2); therefore, the cells were termed BINCs (Brain Iba1(+)/NG2(+) Cells). A bone marrow transplantation experiment using green-fluorescent protein-transgenic rats showed that BINCs were derived from bone marrow. 5-Fluorouracil (5FU) injection at 2 days post reperfusion (2 dpr) markedly reduced the number of BINCs at 7 dpr, causing enlargement of necrotic volumes and frequent death of the rats. When isolated BINCs were transplanted into 5FU-aggravated ischemic lesion, the volume of the lesion was much reduced. Quantitative real-time RT-PCR showed that BINCs expressed mRNAs encoding bFGF, BMP2, BMP4, BMP7, GDNF, HGF, IGF-1, PDGF-A, and VEGF. In particular, BINCs expressed IGF-1 mRNA at a very high level. Immunohistochemical staining showed that IGF-1-expressing BINCs were found not only in rat but also human ischemic brain lesions. These results suggest that bone marrow-derived BINCs play a beneficial role in ischemic brain lesions, at least in part, through secretion of neuroprotective factors.
Smirkin
Anna
A
Department of Molecular and Cellular Physiology, Graduate School of Medicine, Ehime University, Toon, Ehime 791-0295, Japan.
Matsumoto
Hiroaki
H
Takahashi
Hisaaki
H
Inoue
Akihiro
A
Tagawa
Masahiko
M
Ohue
Shiro
S
Watanabe
Hideaki
H
Yano
Hajime
H
Kumon
Yoshiaki
Y
Ohnishi
Takanori
T
Tanaka
Junya
J
D000818:Animals; D000941:Antigens / Q000378:metabolism*; D016026:Bone Marrow Transplantation / Q000502:physiology; D001921:Brain / Q000473:pathology*; D002545:Brain Ischemia / Q000473:pathology*; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D049109:Cell Proliferation; D002544:Cerebral Infarction / Q000473:pathology; D005472:Fluorouracil; D005904:Glial Fibrillary Acidic Protein / Q000378:metabolism; D049452:Green Fluorescent Proteins; D006801:Humans; D007150:Immunohistochemistry; D020244:Infarction, Middle Cerebral Artery / Q000473:pathology; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D008840:Microfilament Proteins; D009457:Neuroglia / Q000378:metabolism; D011509:Proteoglycans / Q000378:metabolism*; D012313:RNA / Q000096:biosynthesis / Q000302:isolation & purification; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D000099216:Chondroitin Sulfate Proteoglycan 4
D000941:Antigens; D001973:Bromodeoxyuridine; D002135:Calcium-Binding Proteins; D005472:Fluorouracil; D005904:Glial Fibrillary Acidic Protein; D049452:Green Fluorescent Proteins; D008840:Microfilament Proteins; D011509:Proteoglycans; D012313:RNA; D000099216:Chondroitin Sulfate Proteoglycan 4; C100745:Aif1 protein, rat