title: Transient ischemia-induced paresis and complete paraplegia displayed distinct reactions of microglia and macrophages.
abstract: In this study, we perform a detailed analysis of the microglial and macrophage responses in a model of spinal cord ischemia and reperfusion (SCI/R) injury in Wistar rats. The rats underwent occlusion across the descending aorta for 13min, causing paraplegia or paresis of varying severity. They were divided into four groups based on neurological assessment: sham, mild paresis, moderate paresis, and severe (complete) paraplegia. To examine the origin of microglia and macrophages in the ischemic lesion, bone marrow from rats expressing green fluorescent protein (GFP) was transplanted into test subjects one month before performing SCI/R. Many GFP(+)/CD68(+) microglia and macrophages were present 7d after SCI/R. Resident (GFP(-)/Iba1(+)/CD68(-)) microglia and bone marrow-derived macrophages (BMDMs; GFP(+)/Iba1(+)/CD68(+)) colocalized in the mild group 7d after SCI/R. In the moderate group, BMDMs outnumbered resident microglia. A greater accumulation of BMDMs expressing insulin-like growth factor-1 (IGF-1) was observed in lesions in the severe group, relative to the moderate group. BMDMs in the severe group strongly expressed tumor necrosis factor α, interleukin-1β, and inducible nitric oxide synthase, in addition to IGF-1. A robust accumulation of BMDMs occupying the entire ischemic gray matter was observed only in the severe group. These results demonstrate that the magnitude of the microglial and BMDM responses varies considerably, and that it correlates with the severity of the neurological dysfunction. Remarkably, BMDMs appear to have a beneficial effect on the spinal cord in paresis. In contrast, BMDMs seem to exhibit both beneficial and harmful effects in severe paraplegia.
authors.affiliation: Department of Cardiothoracic Surgery and Regeneration Surgery, Ehime University Graduate School of Medicine, Toon, Ehime 791-0295, Japan. tatsuhironakata@gmail.com
authors.forename: Tatsuhiro
authors.initials: T
authors.lastname: Nakata
authors.forename: Kanji
authors.initials: K
authors.lastname: Kawachi
authors.forename: Mitsugi
authors.initials: M
authors.lastname: Nagashima
authors.forename: Takumi
authors.initials: T
authors.lastname: Yasugi
authors.forename: Hironori
authors.initials: H
authors.lastname: Izutani
authors.forename: Masahiro
authors.initials: M
authors.lastname: Ryugo
authors.forename: Toru
authors.initials: T
authors.lastname: Okamura
authors.forename: Fumiaki
authors.initials: F
authors.lastname: Shikata
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Imagawa
authors.forename: Hajime
authors.initials: H
authors.lastname: Yano
authors.forename: Hisaaki
authors.initials: H
authors.lastname: Takahashi
authors.forename: Junya
authors.initials: J
authors.lastname: Tanaka
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000235:genetics / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000235:genetics / Q000378:metabolism; D016026:Bone Marrow Transplantation; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D002452:Cell Count; D004195:Disease Models, Animal; D005786:Gene Expression Regulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D002546:Ischemic Attack, Transient / Q000150:complications; D008264:Macrophages / Q000378:metabolism* / Q000473:pathology; D008297:Male; D008562:Membrane Glycoproteins / Q000378:metabolism; D008840:Microfilament Proteins / Q000235:genetics / Q000378:metabolism; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009460:Neurologic Examination; D010264:Paraplegia / Q000209:etiology / Q000473:pathology* / Q000601:surgery; D010291:Paresis / Q000209:etiology / Q000473:pathology* / Q000601:surgery; D051381:Rats; D017207:Rats, Sprague-Dawley; D055647:Rats, Transgenic; D017208:Rats, Wistar; D013997:Time Factors; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D002135:Calcium-Binding Proteins; D049452:Green Fluorescent Proteins; D008562:Membrane Glycoproteins; D008840:Microfilament Proteins; C100745:Aif1 protein, rat; C067980:CD68 antigen, human; D000097382:CD68 Molecule; C028388:thymus-leukemia antigens