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Microglia Proliferate in Striatum and Cortex but not Hippocampus Following Brief Periods of Ischemia that do not Kill Neurons

Frank R. Sharp, Jialing Lu, Matthew N. Bartels, Aigang Lu

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Abstract

61 Because ischemia induced tolerance induces the birth of new neurons following global ischemia, this study determined whether 2.5 minutes of global ischemia and ischemia-induced tolerance would induce the birth of glia in the brain.Following 0, 2.5, or 5 minutes of global ischemia, adult male gerbils were injected with BrdU (50mg/kg) and dividing cells detected using immunocytochemistry. At four days following 2.5 minutes of global ischemia, when cell proliferation was maximal, BrdU labeled cells were detected in striatum and in neocortex, but not in hippocampus. The majority of the BrdU labeled cells were double-labeled with iso-lectin B4, showing that these dividing cells were mainly microglia. Similarly, BrdU labeled microglia were found in striatum and cortex but not in hippocampus of most animals four days following ischemia-induced tolerance (2.5 minutes of global ischemia followed three days later by 5 minutes of global ischemia). Some of the animals subjected to 2.5 minutes of ischemia showed decreased myelin associated glycoprotein (MAG) immunostaining and increased numbers of APC stained oligodendrocytes in the lateral striatum without apparent neuronal loss. Though the CA1 pyramidal and hilar interneurons of hippocampus are the most vulnerable neurons to ischemia, this data suggests that non-neuronal elements in the striatum may be more sensitive to ischemia than the neurons. In some animals proliferation of microglia in striatum following brief global ischemia may occur in response to injury to white matter and oligodendrocytes.

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61 Because ischemia induced tolerance induces the birth of new neurons following global ischemia, this study determined whether 2.5 minutes of global ischemia and ischemia-induced tolerance would induce the birth of glia in the brain.Following 0, 2.5, or 5 minutes of global ischemia, adult male gerbils were injected with BrdU (50mg/kg) and dividing cells detected using immunocytochemistry. At four days following 2.5 minutes of global ischemia, when cell proliferation was maximal, BrdU labeled cells were detected in striatum and in neocortex, but not in hippocampus. The majority of the BrdU labeled cells were double-labeled with iso-lectin B4, showing that these dividing cells were mainly microglia. Similarly, BrdU labeled microglia were found in striatum and cortex but not in hippocampus of most animals four days following ischemia-induced tolerance (2.5 minutes of global ischemia followed three days later by 5 minutes of global ischemia). Some of the animals subjected to 2.5 minutes of ischemia showed decreased myelin associated glycoprotein (MAG) immunostaining and increased numbers of APC stained oligodendrocytes in the lateral striatum without apparent neuronal loss. Though the CA1 pyramidal and hilar interneurons of hippocampus are the most vulnerable neurons to ischemia, this data suggests that non-neuronal elements in the striatum may be more sensitive to ischemia than the neurons. In some animals proliferation of microglia in striatum following brief global ischemia may occur in response to injury to white matter and oligodendrocytes.

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Available abstract

61 Because ischemia induced tolerance induces the birth of new neurons following global ischemia, this study determined whether 2.5 minutes of global ischemia and ischemia-induced tolerance would induce the birth of glia in the brain.Following 0, 2.5, or 5 minutes of global ischemia, adult male gerbils were injected with BrdU (50mg/kg) and dividing cells detected using immunocytochemistry. At four days following 2.5 minutes of global ischemia, when cell proliferation was maximal, BrdU labeled cells were detected in striatum and in neocortex, but not in hippocampus. The majority of the BrdU labeled cells were double-labeled with iso-lectin B4, showing that these dividing cells were mainly microglia. Similarly, BrdU labeled microglia were found in striatum and cortex but not in hippocampus of most animals four days following ischemia-induced tolerance (2.5 minutes of global ischemia followed three days later by 5 minutes of global ischemia). Some of the animals subjected to 2.5 minutes of ischemia showed decreased myelin associated glycoprotein (MAG) immunostaining and increased numbers of APC stained oligodendrocytes in the lateral striatum without apparent neuronal loss. Though the CA1 pyramidal and hilar interneurons of hippocampus are the most vulnerable neurons to ischemia, this data suggests that non-neuronal elements in the striatum may be more sensitive to ischemia than the neurons. In some animals proliferation of microglia in striatum following brief global ischemia may occur in response to injury to white matter and oligodendrocytes.

Key concepts: Ischemia, Microglia, Striatum, Hippocampus, Medicine, Neocortex, Cortex (anatomy), Neuroscience

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