title: Cranial irradiation induces transient microglia accumulation, followed by long-lasting inflammation and loss of microglia.
abstract: The relative contribution of resident microglia and peripheral monocyte-derived macrophages in neuroinflammation after cranial irradiation is not known. A single dose of 8 Gy was administered to postnatal day 10 (juvenile) or 90 (adult) CX3CR1GFP/+ CCR2RFP/+ mouse brains. Microglia accumulated in the subgranular zone of the hippocampal granule cell layer, where progenitor cell death was prominent. The peak was earlier (6 h vs. 24 h) but less pronounced in adult brains. The increase in juvenile, but not adult, brains was partly attributed to proliferation. Microglia numbers then decreased over time to 39% (juvenile) and 58% (adult) of controls 30 days after irradiation, largely as a result of cell death. CD68 was expressed in 90% of amoeboid microglia in juvenile hippocampi but only in 9% of adult ones. Isolated hippocampal microglia revealed reduced CD206 and increased IL1-beta expression after irradiation, more pronounced in juvenile brains. CCL2 and IL-1 beta increased after irradiation, more in juvenile hippocampi, and remained elevated at all time points. In summary, microglia activation after irradiation was more pronounced, protracted and pro-inflammatory by nature in juvenile than in adult hippocampi. Common to both ages was long-lasting inflammation and the absence of monocyte-derived macrophages.
authors: Department of Pediatrics, Henan Provincial Women's and Children's Hospital, Zhengzhou, P.R. China.|Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.|Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors: Wei
authors: W
authors: Han
authors: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.|Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Japan.
authors: Takashi
authors: T
authors: Umekawa
authors: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors: Kai
authors: K
authors: Zhou
authors: Karolinska Institutet, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors: Xing-Mei
authors: XM
authors: Zhang
authors: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors: Makiko
authors: M
authors: Ohshima
authors: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.
authors: Cecilia A
authors: CA
authors: Dominguez
authors: Karolinska Institutet, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden.
authors: Robert A
authors: RA
authors: Harris
authors: Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China.|Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden.
authors: Changlian
authors: C
authors: Zhu
authors: Karolinska Institutet, Department of Women's and Children's Health, Stockholm, Sweden.|Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden.
authors: Klas
authors: K
authors: Blomgren
mesh_terms: D000367:Age Factors; D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D015214:Antigens, Differentiation, Myelomonocytic / Q000378:metabolism; D000073883:CX3C Chemokine Receptor 1 / Q000235:genetics; D016923:Cell Death; D049109:Cell Proliferation / Q000528:radiation effects*; D018932:Chemokine CCL2 / Q000378:metabolism; D016371:Cranial Irradiation / Q000009:adverse effects*; D004660:Encephalitis / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D049452:Green Fluorescent Proteins / Q000235:genetics / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D053583:Interleukin-1beta / Q000378:metabolism; D008164:Luminescent Proteins / Q000235:genetics / Q000378:metabolism; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D017628:Microglia / Q000378:metabolism / Q000473:pathology / Q000528:radiation effects*; D011832:Radiation Injuries / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D054390:Receptors, CCR2 / Q000235:genetics; D013997:Time Factors; D000097573:Red Fluorescent Protein; D000097382:CD68 Molecule
chemical_list: D015703:Antigens, CD; D015214:Antigens, Differentiation, Myelomonocytic; D000073883:CX3C Chemokine Receptor 1; D018932:Chemokine CCL2; D049452:Green Fluorescent Proteins; D053583:Interleukin-1beta; D008164:Luminescent Proteins; D054390:Receptors, CCR2; D000097573:Red Fluorescent Protein; C081026:CD68 protein, mouse; D000097382:CD68 Molecule; C491768:Ccl2 protein, mouse; C515335:Ccr2 protein, mouse; C471885:Cx3cr1 protein, mouse; C587672:IL1B protein, mouse
keywords: irradiation; macrophage; microglia; monocyte; neurogenesis; neuroinflammation