Oncotarget

Research Papers:

Cranial irradiation induces transient microglia accumulation, followed by long-lasting inflammation and loss of microglia

Wei Han, Takashi Umekawa, Kai Zhou, Xing-Mei Zhang, Makiko Ohshima, Cecilia A. Dominguez, Robert A. Harris, Changlian Zhu and Klas Blomgren _

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Oncotarget. 2016; 7:82305-82323. https://doi.org/10.18632/oncotarget.12929

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Abstract

Wei Han1,2,3, Takashi Umekawa3,4, Kai Zhou3, Xing-Mei Zhang5, Makiko Ohshima3, Cecilia A. Dominguez3, Robert A. Harris5, Changlian Zhu2,6 and Klas Blomgren3,7

1 Department of Pediatrics, Henan Provincial Women’s and Children’s Hospital, Zhengzhou, P.R. China

2 Henan Key Laboratory of Child Brain Injury, The Third Affiliated Hospital of Zhengzhou University, Zhengzhou, P.R. China

3 Karolinska Institutet, Department of Women’s and Children’s Health, Stockholm, Sweden

4 Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, Tsu, Japan

5 Karolinska Institutet, Department of Clinical Neuroscience, Center for Molecular Medicine, Karolinska University Hospital, Stockholm, Sweden

6 Center for Brain Repair and Rehabilitation, Institute of Neuroscience and Physiology, University of Gothenburg, Gothenburg, Sweden

7 Department of Pediatric Oncology, Karolinska University Hospital, Stockholm, Sweden

Correspondence to:

Klas Blomgren, email:

Changlian Zhu, email:

Keywords: irradiation, neurogenesis, neuroinflammation, microglia, monocyte, macrophage

Received: August 11, 2016 Accepted: October 13, 2016 Published: October 26, 2016

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.


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