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Title: Effects of Oxygen Glucose Deprivation and Recovery on Polarization of Microglia in Primary Culture and Effects on Astrocytes of these Processes
Authors: Rawan Muneer Ishak Barakat 
Supervisor: Prof. Zoran Redzic
Keywords: Cerebral ischemia;microglia;astrocytes;apoptosis;necrosis;M1 phenotype;M2 phenotype
Issue Date: 2015
Publisher:  Kuwait university - college of graduate studies
Abstract: Activation of microglia/macrophages following cerebral ischemia may be beneficial or detrimental for survival of brain cells. This ambiguity was explained by findings that ischemia induces transformation of the microglia/macrophages into two different phenotypes, a process often referred to as polarization into M1 and M2 phenotypes. To which extent these processes depend on paracrine signaling from other cells of the neurovascular unit (NVU) is not clear. The aim of this in vitro study was to explore if polarization of these cells into the two phenotypes could occur in absence/low abundance of other NVU cells, and to assess effect of microglia/macrophages-derived cytokines on astrocytes' viability during anoxia. Primary cultures of rat microglia/macrophages were exposed to 2 hours of oxygen glucose deprivation (OGD) and then incubated further under normal conditions, which was considered as a recovery period. Expression of phenotype-specific markers at transcript and protein levels and secretion of phenotype-specific cytokines were explored at different time points of the recovery period by Real-time PCR, immunohistochemistry and ELISA, respectively. Astrocytes' viability was explored in the presence or absence of phenotype-specific cytokines during anoxia or in control conditions. OGD protocol has triggered an increase in expression/secretion of M2-specific markers/cytokines, with a similar time-pattern as revealed after ischemia in vivo. Expression/secretion of M1-specific markers/cytokines did not show a common time-pattern, but there was a general tendency for an increase during the recovery period. Well-known pharmacological protocols for induction of the M1 and M2 phenotypes have caused secretion of cytokines that were consistent with polarization of these cells into M1 phenotype and polarization into mixed (M1 and M2) phenotypes, respectively. Surprisingly, all M1-specific and two out of the three tested M2-specific cytokines revealed protective effects on astrocytes during anoxia. Polarization of the brain microglia/macrophages into M2 phenotype could be triggered by OGD in vitro, so it appeared that this process was largely independent from paracrine signaling of NVU cells. On the other hand, no clear polarization into M1 phenotype after OGD or shift of M2 into M1 phenotype, processes that were described after ischemia in vivo, could be confirmed in vitro, so it appeared that they depended to a greater extent on paracrine signaling from other NVU cells. Cytokines that were released from polarized microglia were protective for astrocytes during anoxia.
Appears in Programs:0530 Physiology (M.Sc.)

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