title: Microglia/macrophages proliferate in striatum and neocortex but not in hippocampus after brief global ischemia that produces ischemic tolerance in gerbil brain.
abstract: The current study determined whether short durations of ischemia that produce ischemia-induced tolerance stimulate glial proliferation in brain. Adult male gerbils were injected with BrdU (50 mg/kg) and dividing cells were detected using immunocytochemistry after sham operations, 2.5 or 5 minutes of global ischemia, or ischemia-induced tolerance. The 2.5-minute ischemia and the ischemia-induced tolerance did not kill hippocampal CA1 pyramidal neurons, whereas the 5-minute ischemia did kill the neurons. At 4 days after 2.5-minute global ischemia, when cell proliferation was maximal, BrdU-labeled cells increased in striatum and in neocortex, but not in hippocampus. The majority of the BrdU-labeled cells were double-labeled with isolectin B4, showing that these dividing cells were primarily microglia or macrophages, or both. Similarly, BrdU-labeled microglia/macrophages were found in striatum and neocortex but not in hippocampus of most animals 4 days after ischemia-induced tolerance (2.5 minutes of global ischemia followed 3 days later by 5 minutes of global ischemia). No detectable neuronal cell death existed in striatal and cortical regions where the microglia/macrophage proliferation occurred. Though 3 of 7 animals subjected to 2.5 minutes of ischemia showed decreased myelin-associated glycoprotein (MAG) immunostaining and increased numbers of adenomatous polyposis coli-stained oligodendrocytes in lateral striatum, this did not explain the microglia/macrophage proliferation. Data show that ischemia-induced tolerance in the gerbil is associated with proliferation of microglia/macrophages in striatum and cortex but not in hippocampus. Because there is no apparent neuronal death, it is postulated that the microglia/macrophage proliferation occurs in response to an unknown nonlethal injury to neurons or glia and may be beneficial.
authors.affiliation: Department of Neurology, University of California at San Francisco, San Francisco, California, USA.
authors.forename: J
authors.initials: J
authors.lastname: Liu
authors.forename: M
authors.initials: M
authors.lastname: Bartels
authors.forename: A
authors.initials: A
authors.lastname: Lu
authors.forename: F R
authors.initials: FR
authors.lastname: Sharp
mesh_terms: D025601:Adenomatous Polyposis Coli Protein; D000818:Animals; D001921:Brain / Q000166:cytology*; D001973:Bromodeoxyuridine / Q000032:analysis; D002455:Cell Division / Q000502:physiology; D003342:Corpus Striatum / Q000166:cytology; D003598:Cytoskeletal Proteins / Q000032:analysis; D005849:Gerbillinae; D006624:Hippocampus / Q000166:cytology; D002546:Ischemic Attack, Transient / Q000473:pathology*; D037102:Lectins; D008264:Macrophages / Q000166:cytology*; D008297:Male; D017628:Microglia / Q000166:cytology*; D018992:Myelin-Associated Glycoprotein / Q000032:analysis; D019579:Neocortex / Q000166:cytology; D009413:Nerve Fibers, Myelinated / Q000737:chemistry; D009836:Oligodendroglia / Q000166:cytology; D020521:Stroke / Q000473:pathology
chemical_list: D025601:Adenomatous Polyposis Coli Protein; D003598:Cytoskeletal Proteins; D037102:Lectins; D018992:Myelin-Associated Glycoprotein; D001973:Bromodeoxyuridine