Progressive expression of immunomolecules on activated microglia and invading leukocytes following focal cerebral ischemia in the rat.
In order to evaluate the involvement of inflammatory reactions following focal cerebral ischemia in the rat, we immunohistochemically visualized microglial cells and blood-borne leukocytes (neutrophils and monocytes) using various antibodies directed against immunomolecules expressed on these cells. Focal cerebral ischemia was produced by intraluminal occlusion of the right middle cerebral artery for 1 h. The brains were perfusion-fixed at 4 h, 1 day, 3 days, 7 days and 14 days after ischemia. Frozen brain sections were prepared and stained with monoclonal antibodies to complement receptor type 3 (OX42), major histocompatibility complex (MHC) class I and class II antigens (OX18 and OX6, respectively), a pan-macrophage/monocyte marker (ED1), intercellular adhesion molecule-1 (ICAM-1), LFA-1 alpha chain (CD11a) and beta chain (CD18), and T cells (CD5). In ischemic areas where infarction developed later, microglial cells were destroyed (beginning at 4 h), neutrophils migrated (1-3 days), and then monocytes/macrophages infiltrated and covered the entire lesions (3-14 days). The invading leukocytes expressed CD11 and CD18 adhesion molecules on their cell surface while ICAM-1 was expressed on endothelial cells. In surrounding areas, in contrast, there was a rapid activation of microglia showing morphological changes and upregulation of OX42 immunoreactivity (4 h-7 days), especially in the transitional rim of the infarct (7 days). ED1 and MHC antigens were expressed on both activated microglia and invading leukocytes. Thus, developing infarction was accompanied by accumulation of inflammatory cells of both intrinsic (microglia) and extrinsic (leukocytes) origins. Thus, results suggest that the relative importance of each source is determined by the time after ischemia and the site within the lesion, and that the expression of immunological molecules plays an important role in eliciting such inflammatory reactions.
Kato
H
H
Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
Kogure
K
K
Liu
X H
XH
Araki
T
T
Itoyama
Y
Y
D000818:Animals; D000941:Antigens / Q000032:analysis*; D015703:Antigens, CD / Q000032:analysis; D015415:Biomarkers; D002545:Brain Ischemia / Q000276:immunology* / Q000473:pathology / Q000503:physiopathology; D002465:Cell Movement; D006649:Histocompatibility Antigens / Q000032:analysis; D007150:Immunohistochemistry; D007962:Leukocytes / Q000276:immunology* / Q000502:physiology; D008297:Male; D017628:Microglia / Q000276:immunology* / Q000502:physiology; D051381:Rats; D017208:Rats, Wistar
D000941:Antigens; D015703:Antigens, CD; D015415:Biomarkers; D006649:Histocompatibility Antigens