title: Direct comparison of microglial dynamics and inflammatory profile in photothrombotic and arterial occlusion evoked stroke.
abstract: Many focal cerebral ischemia models utilize the middle cerebral artery occlusion (MCAO) evoked by coagulation to induce ischemic damage in the cortex and mimic the pathology observed in human patients. A second, increasingly popular model, the photothrombotic stroke, uses a laser beam to irradiate the MCA after administration of a photosensitizing dye. This widely used procedure is slowly replacing the MCAO model because of the easiness of the surgical protocol and the reproducibility of the damage. However, the photochemical reaction also results in wider microvascular injury. In this study, we have evaluated the impact of these two types of stroke in the cell survival and evolution of stroke, focusing on microglial cells, the first responders to cell injury. Two groups of heterozygote Cx3CR1-GFP reporter mice (to follow microglia) were subject to stroke injury either with coagulator-mediated occlusion or photothrombotic MCA damage. Microglial cells' dynamics of activation and phagocytosis together with astrocytic response and leukocyte infiltration were characterized at 1, 3 and 7days after damage. Photothrombotic stroke delayed microglial and astrocytic invasion of the ischemic core and accumulation of phagocytic microglia. It also elicited higher levels of inflammatory cytokines/chemokines and increased infiltration from the periphery. In addition, only the neurons in the MCAO stroke showed phenotype plasticity by downregulating the transcription factor NeuN. These data provide a better understanding of the exact temporal and spatial dynamics of the inflammatory response in these two animal models of stroke and identify more relevant targets for human therapy.
authors.affiliation: Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, NY 14640, USA.
authors.forename: Maria L
authors.initials: ML
authors.lastname: Cotrina
authors.affiliation: Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, NY 14640, USA.
authors.forename: Nanghong
authors.initials: N
authors.lastname: Lou
authors.affiliation: Department of Pathology, Icahn School of Medicine at Mount Sinai, New York, NY, USA; Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
authors.forename: Jessica
authors.initials: J
authors.lastname: Tome-Garcia
authors.affiliation: Department of Pathology, Columbia University Medical Center, USA.
authors.forename: James
authors.initials: J
authors.lastname: Goldman
authors.affiliation: Division of Glia Disease and Therapeutics, Center for Translational Neuromedicine, University of Rochester Medical School, Rochester, NY 14640, USA.
authors.forename: Maiken
authors.initials: M
authors.lastname: Nedergaard
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D002545:Brain Ischemia / Q000209:etiology / Q000276:immunology / Q000473:pathology; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics / Q000378:metabolism; D004268:DNA-Binding Proteins; D004195:Disease Models, Animal; D018450:Disease Progression; D004558:Electric Stimulation; D005260:Female; D005911:Gliosis / Q000209:etiology / Q000276:immunology / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D007834:Lasers; D007962:Leukocytes / Q000378:metabolism / Q000473:pathology; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism* / Q000473:pathology; D009419:Nerve Tissue Proteins / Q000378:metabolism; D009474:Neurons / Q000276:immunology / Q000473:pathology; D009687:Nuclear Proteins / Q000378:metabolism; D010587:Phagocytosis / Q000502:physiology; D020521:Stroke / Q000209:etiology* / Q000276:immunology* / Q000473:pathology; D013997:Time Factors
chemical_list: D000073883:CX3C Chemokine Receptor 1; C471885:Cx3cr1 protein, mouse; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C492380:NeuN protein, mouse; D009687:Nuclear Proteins; D049452:Green Fluorescent Proteins
keywords: astrocytes; inflammation; ischemia; microglia; photothrombosis; stroke