C-C Chemokine Receptor 5 (CCR5) Expression in the Infarct Brain of the Photothrombosis Mouse Model

DOI Web Site 被引用文献2件 参考文献22件
  • Hasegawa Hiroshi
    Laboratory of Hygienic Sciences, Kobe Pharmaceutical University
  • Kondo Mari
    Laboratory of Hygienic Sciences, Kobe Pharmaceutical University
  • Hohjoh Hirofumi
    Laboratory of Hygienic Sciences, Kobe Pharmaceutical University
  • Nakayama Kei
    Laboratory of Hygienic Sciences, Kobe Pharmaceutical University
  • Segi-Nishida Eri
    Department of Biological Science and Technology, Faculty of Industrial Science and Technology, Tokyo University of Science

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<p>Brain ischemic stroke is one of the leading causes of death in developed countries, including Japan. Controlling the neuroinflammation in the penumbra region with mild ischemia is crucial for treating ischemic stroke. C-C chemokine receptor 5 (CCR5), noted for its functions in the progression of neuroinflammation, is considered a promising drug target. We recently found that three CCR5-regulated matrix metalloproteinases (MMPs) are detected in various cell types, including neurons, microglia, and blood vessel endothelial cells, in the ischemic brain of the photothrombosis model mouse. However, it is still unclear whether CCR5 is expressed in these cell types. This study examined the presence of CCR5 in the photothrombotic brain. Preceding the analysis, we evaluated and improved the photothrombosis induction protocol to obtain equable results with lower toxicity. Rose bengal, used to induce thrombosis to cause an infarction, is radicalized by laser and exhibits pancreatic toxicity. Therefore, we changed the administration route from the abdomen to the jugular vein and reduced the required dose of rose bengal. With this improved protocol, we found that the level of CCR5 protein was increased in neurons, microglia, and blood vessels in the ischemic core, in the infarct brain. The increase in CCR5 levels was sensitive to NSAIDs, especially to cyclooxygenase-2-selective etodolac. CD4, a collaborative membrane receptor for CCR5, was also detected in the migrating microglia. These results suggest that CCR5 is dynamically regulated and play diverse roles during ischemic stroke.</p>

収録刊行物

  • BPB Reports

    BPB Reports 3 (6), 208-215, 2020

    公益社団法人 日本薬学会

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