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Increased CD68/TGFβ Co-expressing Microglia/ Macrophages after Transient Middle Cerebral Artery Occlusion in Rhesus Monkeys

Experimental Neurobiology 2019년 28권 4호 p.458 ~ 473
 ( Yeo Hyeon-Gu ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center

 ( Hong Jung-Joo ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Lee Young-Jeon ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Yi Kyung-Sik ) - Chungbuk National University Hospital Department of Radiology
 ( Jeon Chang-Yeop ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Park Jung-Hyung ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Won Jin-Young ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Seo Jin-Cheol ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Ahn Yu-Jin ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Kim Keon-Woo ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Baek Seung-Ho ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Hwang Eun-Ha ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Kim Green ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Jin Yeung-Bae ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Jeong Kang-Jin ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Koo Bon-Sang ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Kang Phil-Yong ) - Korea Research Institute of Bioscience and Biotechnology Futuristic Animal Resource and Research Center
 ( Lim Kyung-Seob ) - Korea Research Institute of Bioscience and Biotechnology Futuristic Animal Resource and Research Center
 ( Kim Sun-Uk ) - Korea Research Institute of Bioscience and Biotechnology Futuristic Animal Resource and Research Center
 ( Huh Jae-Won ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Kim Young-Hyun ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center
 ( Son Yeong-Hoon ) - Korea Research Institute of Bioscience and Biotechnology Primate Resource Center
 ( Kim Ji-Su ) - Korea Research Institute of Bioscience and Biotechnology Primate Resource Center
 ( Choi Chi-Hoon ) - Chungbuk National University Hospital Department of Radiology
 ( Cha Sang-Hoon ) - Chungbuk National University Hospital Department of Radiology
 ( Lee Sang-Rae ) - Korea Research Institute of Bioscience and Biotechnology National Primate Research Center

Abstract


The function of microglia/macrophages after ischemic stroke is poorly understood. This study examines the role of microglia/macrophages in the focal infarct area after transient middle cerebral artery occlusion (MCAO) in rhesus monkeys. We measured infarct volume and neurological function by magnetic resonance imaging (MRI) and non-human primate stroke scale (NHPSS), respectively, to assess temporal changes following MCAO. Activated phagocytic microglia/macrophages were examined by immunohistochemistry in post-mortem brains (n=6 MCAO, n=2 controls) at 3 and 24 hours (acute stage), 2 and 4 weeks (subacute stage), and 4, and 20 months (chronic stage) following MCAO. We found that the infarct volume progressively decreased between 1 and 4 weeks following MCAO, in parallel with the neurological recovery. Greater presence of cluster of differentiation 68 (CD68)-expressing microglia/macrophages was detected in the infarct lesion in the subacute and chronic stage, compared to the acute stage. Surprisingly, 98~99% of transforming growth factor beta (TGFβ) was found colocalized with CD68-expressing cells. CD68-expressing microglia/macrophages, rather than CD206+ cells, may exert anti-inflammatory effects by secreting TGFβ after the subacute stage of ischemic stroke. CD68+ microglia/macrophages can therefore be used as a potential therapeutic target.

키워드

Inflammation; Microglia; Stroke; Macaca mulatta; Transforming growth factor beta
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