Microglia/macrophages proliferate in striatum and neocortex by not in hippocampus after brief global ischemia that produces ischemic tolerance in gerbil brain

The current study determined whether short durations of ischemia that produ ce ischemia-induced tolerance stimulate glial proliferation in brain. Adult male gerbils were injected with BrdU (50 mg/kg) and dividing cells were de tected using immunocytochemistry after sham operations, 2.5 or 5 minutes of global ischemia, or ischemia-induced tolerance. The 2.5-minute ischemia an d the ischemia-induced tolerance did not kill hippocampal CA1 pyramidal neu rons, whereas the 5-minute ischemia did kill the neurons. At 4 days after 2 .5-minute global ischemia, when cell proliferation was maximal, BrdU-labele d 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 striat um and neocortex but not in hippocampus of most animals 4 days after ischem ia-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 proliferat ion occurred. Though 3 of 7 animals subjected to 2.5 minutes of ischemia sh owed decreased myelin-associated glycoprotein (MAG) immunostaining and incr eased numbers of adenomatous polyposis coli-stained oligodendrocytes in lat eral 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 h ippocampus. Because there is no apparent neuronal death, it is postulated t hat the microglia/macrophage proliferation occurs in response to an unknown nonlethal injury to neurons or plia and may be beneficial.