Progressive expression of immunomolecules on microglial cells in rat dorsal hippocampus following transient forebrain ischemia.
We show a differential up-regulation of immunomolecules in the rat dorsal hippocampus accompanying neuronal cell death as a consequence of transient forebrain ischemia (four-vessel occlusion model). Using a panel of monoclonal antibodies (mAbs), we have examined the time course of expression of major histocompatibility complex (MHC) antigens class I (OX-18) and class II (OX-6), leukocyte common antigen (OX-1), CD4 (W3/25) and CD8 (OX-8) antigens, CR3 complement receptor (OX-42), as well as brain macrophage antigen (ED2). The study was performed at time intervals ranging from 1 to 28 days after reperfusion. Throughout all post-ischemic time periods, strongly enhanced immunoreactivity on microglial cells in the CA1 region and dentate hilus and, to a lesser extent, in CA3 was demonstrated with mAb OX-42. MHC class I-positive cells (OX-18) appeared on day 2, whereas cells immunoreactive with OX-1 and W3/25 became evident in the CA1 and hilar regions on post-ischemic day 6. In contrast, MHC class II (Ia) antigen was first detected on indigenous microglia by day 13. In some animals, the OX-8 antibody resulted in the labelling of scattered CD8-positive lymphocytes, but perivascular inflammatory infiltrates were absent. No changes in the expression of ED2 immunoreactivity on perivascular cells could be observed. The results show that following ischemic injury, microglial cells demonstrate a time-dependent up-regulation and de novo expression of certain immunomolecules, indicative of their immunocompetence. The findings are compared with those obtained in other models of brain injury.
Morioka
T
T
Department of Neurological Surgery, University of Florida Health Science Center, Gainesville 32610-0244.
Kalehua
A N
AN
Streit
W J
WJ
D000818:Animals; D000911:Antibodies, Monoclonal; D015704:CD4 Antigens / Q000276:immunology; D016827:CD8 Antigens / Q000276:immunology; D003176:Complement C3 / Q000378:metabolism; D005260:Female; D006624:Hippocampus / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D015395:Histocompatibility Antigens Class I / Q000276:immunology; D000949:Histocompatibility Antigens Class II / Q000276:immunology; D002546:Ischemic Attack, Transient / Q000276:immunology / Q000378:metabolism*; D008214:Lymphocytes / Q000276:immunology; D009457:Neuroglia / Q000276:immunology / Q000378:metabolism*; D016548:Prosencephalon / Q000276:immunology / Q000378:metabolism*; D051381:Rats; D011919:Rats, Inbred Strains; D011951:Receptors, Complement / Q000378:metabolism; D015854:Up-Regulation
D000911:Antibodies, Monoclonal; D015704:CD4 Antigens; D016827:CD8 Antigens; D003176:Complement C3; D015395:Histocompatibility Antigens Class I; D000949:Histocompatibility Antigens Class II; D011951:Receptors, Complement