title: Graded expression of immunomolecules on activated microglia in the hippocampus following ischemia in a rat model of ischemic tolerance.
abstract: Preconditioning of the brain with sublethal ischemia protects against neuronal damage following subsequent longer periods of ischemia (ischemic tolerance). In order to evaluate the potential involvement of microglial activation in ischemic tolerance, we immunohistochemically visualized microglial cells in the hippocampus in a rat model of ischemic tolerance. Three minutes of forebrain ischemia (preconditioning ischemia) or sham operation was followed by 6 min of ischemia (second ischemia) 3 days later. The brains were perfusion-fixed after 2 h, 1 day, 3 days, and 7 days. Microglial cells were localized by histochemical staining with isolectin-B4 from Griffonia simplicifolia and by immunohistochemistry of immunomolecules with monoclonal antibodies against major histocompatibility complex class I (OX18) and class II (OX6) antigens and complement receptor type 3 (OX42) and with a rat macrophage marker ED1 and a pan-T cell marker W3/13. Quiescent microglia were stained only by OX42. Preconditioning ischemia led to moderate microglial activation as shown by staining with isolectin, OX42, and OX18. Six minutes of ischemia (without preconditioning) caused early generalized microglial activation as shown by lectin and OX42 after 2 h and by OX18 after 1 day. This length of ischemia produced CA1 neuronal destruction after 3 and 7 days when we observed phagocytic transformation of microglia and increased expression of immunomolecules including OX6 and ED1 However, no staining was seen with W3/13. Following 6-min ischemia with preconditioning, early microglial activation was observed with lectin, OX42, and OX18, but CA1 neuronal damage was prevented and the microglial activation returned toward normal after 7 days. Thus, activation of microglia and expression of immunomolecules occurred in a graded and controlled fashion in response to different degrees of neuronal injury.
authors.affiliation: Department of Neurology, Tohoku University School of Medicine, Sendai, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Kato
authors.forename: K
authors.initials: K
authors.lastname: Kogure
authors.forename: T
authors.initials: T
authors.lastname: Araki
authors.forename: Y
authors.initials: Y
authors.lastname: Itoyama
mesh_terms: D000222:Adaptation, Physiological; D000818:Animals; D002545:Brain Ischemia / Q000378:metabolism* / Q000473:pathology; D018891:Dentate Gyrus / Q000378:metabolism / Q000473:pathology; D006624:Hippocampus / Q000378:metabolism* / Q000473:pathology; D007150:Immunohistochemistry; D008297:Male; D017628:Microglia / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar