The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice.
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The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice. / Gelderblom, Mathias; Leypoldt, Frank; Lewerenz, Jan; Birkenmayer, Gabriel; Orozco, Denise; Ludewig, Peter; Thundyil, John; Arumugam, Thiruma V; Gerloff, Christian; Tolosa, Eva; Maher, Pamela; Magnus, Tim.
in: J CEREBR BLOOD F MET, Jahrgang 32, Nr. 5, 5, 2012, S. 835-843.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - The flavonoid fisetin attenuates postischemic immune cell infiltration, activation and infarct size after transient cerebral middle artery occlusion in mice.
AU - Gelderblom, Mathias
AU - Leypoldt, Frank
AU - Lewerenz, Jan
AU - Birkenmayer, Gabriel
AU - Orozco, Denise
AU - Ludewig, Peter
AU - Thundyil, John
AU - Arumugam, Thiruma V
AU - Gerloff, Christian
AU - Tolosa, Eva
AU - Maher, Pamela
AU - Magnus, Tim
PY - 2012
Y1 - 2012
N2 - The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor ? (TNF?) production. Fisetin also inhibited LPS-induced TNF? production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor ?B activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia.
AB - The development of the brain tissue damage in ischemic stroke is composed of an immediate component followed by an inflammatory response with secondary tissue damage after reperfusion. Fisetin, a flavonoid, has multiple biological effects, including neuroprotective and antiinflammatory properties. We analyzed the effects of fisetin on infarct size and the inflammatory response in a mouse model of stroke, temporary middle cerebral artery occlusion, and on the activation of immune cells, murine primary and N9 microglial and Raw264.7 macrophage cells and human macrophages, in an in vitro model of inflammatory immune cell activation by lipopolysaccharide (LPS). Fisetin not only protected brain tissue against ischemic reperfusion injury when given before ischemia but also when applied 3 hours after ischemia. Fisetin also prominently inhibited the infiltration of macrophages and dendritic cells into the ischemic hemisphere and suppressed the intracerebral immune cell activation as measured by intracellular tumor necrosis factor ? (TNF?) production. Fisetin also inhibited LPS-induced TNF? production and neurotoxicity of macrophages and microglia in vitro by suppressing nuclear factor ?B activation and JNK/Jun phosphorylation. Our findings strongly suggest that the fisetin-mediated inhibition of the inflammatory response after stroke is part of the mechanism through which fisetin is neuroprotective in cerebral ischemia.
KW - Animals
KW - Humans
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Cell Line
KW - Anti-Inflammatory Agents/pharmacology
KW - Tumor Necrosis Factor-alpha/immunology/metabolism
KW - Brain Infarction/immunology/metabolism/pathology
KW - Dendritic Cells/immunology/metabolism/pathology
KW - Flavonoids/pharmacology
KW - Infarction, Middle Cerebral Artery/immunology/metabolism/pathology
KW - JNK Mitogen-Activated Protein Kinases/immunology/metabolism
KW - Lipopolysaccharides/toxicity
KW - MAP Kinase Kinase 4/immunology/metabolism
KW - Macrophages/immunology/metabolism/pathology
KW - Microglia/immunology/metabolism/pathology
KW - Neuroprotective Agents/pharmacology
KW - Phosphorylation/drug effects
KW - Reperfusion Injury/immunology/metabolism/pathology
KW - Animals
KW - Humans
KW - Time Factors
KW - Disease Models, Animal
KW - Mice
KW - Cell Line
KW - Anti-Inflammatory Agents/pharmacology
KW - Tumor Necrosis Factor-alpha/immunology/metabolism
KW - Brain Infarction/immunology/metabolism/pathology
KW - Dendritic Cells/immunology/metabolism/pathology
KW - Flavonoids/pharmacology
KW - Infarction, Middle Cerebral Artery/immunology/metabolism/pathology
KW - JNK Mitogen-Activated Protein Kinases/immunology/metabolism
KW - Lipopolysaccharides/toxicity
KW - MAP Kinase Kinase 4/immunology/metabolism
KW - Macrophages/immunology/metabolism/pathology
KW - Microglia/immunology/metabolism/pathology
KW - Neuroprotective Agents/pharmacology
KW - Phosphorylation/drug effects
KW - Reperfusion Injury/immunology/metabolism/pathology
M3 - SCORING: Journal article
VL - 32
SP - 835
EP - 843
JO - J CEREBR BLOOD F MET
JF - J CEREBR BLOOD F MET
SN - 0271-678X
IS - 5
M1 - 5
ER -
