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  • [J Med Chem.] Gadolinium-Based Neuroprognostic Magnetic Resonance Imaging Agents Suppress COX-2 for Prevention of Reperfusion Injury after Stroke

    경북대 / 김희경, 장용민*

  • 출처
    J Med Chem.
  • 등재일
    2020 Jul 9
  • 저널이슈번호
    63(13):6909-6923. doi: 10.1021/acs.jmedchem.0c00285. Epub 2020 Jun 25.
  • 내용

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    Abstract
    Advancements in recanalization therapies have rendered reperfusion injury an important challenge for stroke management. It is essential to work toward effective therapeutics that protect the ischemic brain from reperfusion injury. Here, we report a new concept of neuroprognostic agents, which combine molecular diagnostic imaging and targeted neuroprotection for treatment of reperfusion injury after stroke. These neuroprognostic agents are inflammation-targeted gadolinium compounds conjugated with nonsteroidal anti-inflammatory drugs (NSAIDs). Our results demonstrated that gadolinium-based MRI contrast agents conjugated with NSAIDs suppressed the increase in cyclooxygenase-2 (COX-2) levels, ameliorated glial activation, and neuron damage that are phenotypic for stroke by mitigating neuroinflammation, which prevented reperfusion injury. In addition, this study showed that the neuroprognostic agents are promising T1 molecular MRI contrast agents for detecting precise reperfusion injury locations at the molecular level. Our results build on this new concept of neuroprognostics as a novel management strategy for ischemia-reperfusion injury, combining neuroprotection and molecular diagnostics.

     

     

    Affiliations

    Hee-Kyung Kim  1   2 , Jung-Jin Lee  3 , Garam Choi  3   4 , Bokyung Sung  4 , Yeoun-Hee Kim  3 , Ah Rum Baek  4 , Soyeon Kim  4 , Huijin Song  2 , Minsup Kim  5 , Art E Cho  5 , Gang Ho Lee  6 , Sungjun Moon  7 , Min-Kyoung Kang  8 , Jae Jun Lee  8 , Yongmin Chang  4   9   10
    1 BK21 Plus KNU Biomedical Convergence Program, School of Medicine, Kyungpook National University, 41944 Daegu, Korea.
    2 Institute of Biomedical Engineering Research, Kyungpook National University, 41944 Daegu, Korea.
    3 Department of R & D Center, Myungmoon Bio. Co., Hwaseong, 18622 Gyeonggi-do, Korea.
    4 Department of Medical & Biological Engineering, Kyungpook National University, 41944 Daegu, Korea.
    5 Department of Bioinformatics, Korea University, 30019 Sejong, Korea.
    6 Department of Chemistry, Kyungpook National University, 41566 Daegu, Korea.
    7 Department of Radiology, Yeungnam University Medical Center, 42415 Daegu, Korea.
    8 Laboratory Animal Center, KBIO Osong Medical Innovation Foundation, 28160 Osong, Korea.
    9 Department of Radiology, Kyungpook National University Hospital, 41944 Daegu, Korea.
    10 Department of Molecular Medicine, School of Medicine, Kyungpook National University, 41944 Daegu, Korea.

  • 편집위원

    이 논문은 허혈재관류 손상(ischemia-reperfusion injury) 예방 및 MRI 영상이 동시에 가능한 물질을 개발하고 이를 이용한 동물실험 결과를 보여주고 있다. 이 약제는 Gd(III) MRI 영상제제와 nonsteroidal anti-inflammatory drugs(NSAIDs)을 결합한 것으로, 좋은 T1 MRI 조영제로써의 역할과 함께 cyclooxygenase-1(COX-2) 효소 증가를 억제시키며 신경 교세포 활성화 및 신경 손상을 개선하는 결과를 동물 실험을 통해 제시하고 있다.

    2020-08-26 15:59:20

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