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Heterogeneity of the microglial response in photochemically induced focal ischemia of the rat cerebral cortex.
Authors:M Schroeter  S Jander  O W Witte  G Stoll
Institution:1. Institute of Clinical Neuroimmunology, University Hospital, Ludwig-Maximilians Universität München, Munich, Germany;2. Biomedical Center (BMC), Faculty of Medicine, Ludwig-Maximilians Universität München, Martinsried, Germany;3. Institute of Neuronal Cell Biology, Technische Universität München, Munich, Germany;4. Munich Cluster for Systems Neurology (SyNergy), Munich, Germany;5. German Center for Neurodegenerative Diseases (DZNE), Munich, Germany;6. Center of Integrated Protein Science (CIPSM), Munich, Germany;1. State Key Laboratory of Natural Medicines, School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing 210009, PR China;2. School of Sciences, China Pharmaceutical University, Nanjing 210009, PR China;3. Jiangsu Jinglixin Pharmaceutical Technology Company Limited, Nanjing 211100, PR China;4. Medicine & Chemical Institute, China Pharmaceutical University, Nanjing 210009, PR China;1. Department of Pediatric Immunology, School of Medicine, Erciyes University, Kayseri, Turkey;2. Medical Faculty, Department of Pediatric Intensive Care Unit, Erciyes University, Kayseri, Turkey;3. Medical Faculty, Department of Pediatric Radiology, Erciyes University, Kayseri, Turkey;4. Department of Erasmus MC, University Medical Center Rotterdam, Rotterdam, the Netherlands;5. Medical Faculty, Department of Pediatric Nephrology, Erciyes University, Kayseri, Turkey;2. International Clinical Research Centre, Stroke Research Program, St. Anne´s University Hospital, Brno, Czech Republic;3. Institute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic;4. Departments of Clinical Neurosciences, Calgary Stroke Program, Cumming School of Medicine, University of Calgary, Calgary, Canada;5. Division of Interventional Neuroradiology, David Geffen School of Medicine, University of California, Los Angeles, California
Abstract:This study examined microglial responses after photochemically induced focal ischemia of the rat cortex. Microglial activation exceeded by far the area of the ischemic lesion. Based on morphological criteria and expression of immunomolecules three distinct patterns could be distinguished. (1) In the infarct core and the border zone microglia transformed into phagocytes and removed debris with the aid of hematogeneous macrophages. Exclusively in this area a subpopulation of CD8+ microglia/mnacrophages was present. (2) In secondarily degenerating fibre tracts and nuclei with retrograde neuronal loss, microglia were activated with a delay of days and showed increased expression of complement receptor 3, major histocompatibility complex class II and CD4 molecules, but only low phagocytic activity. (3) In remote ipsilateral cortex devoid of neuronal damage, microglia transiently responded by increased complement receptor 3, but not by major histocompatibility complex class II and CD4 expression. Furthermore, the total number of microglia had increased. This remote response could partly be blocked by dizocilpine maleate, a non-competitive N-methyl-D-aspartate receptor antagonist, implicating a functional role of spreading depression. Taken together, our findings point to a tight and differential regulation of microglial responses in the infarct core, degenerating fibre tracts and remote brain regions without neuronal loss.
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