The Korean Journal of Physiology and Pharmacology

  • 제28권3호
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  • Pages.239-252
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  • 2024
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  • 1226-4512(pISSN)
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  • 2093-3827(eISSN)
대한약리학회 (The Korean Society of Pharmacology)
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Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling

  • Canmin Zhu (Department of Neurology, The First People's Hospital of Jiangxia District) ;
  • Dili Wang (Department of Neurology, The First People's Hospital of Jiangxia District) ;
  • Chang Chang (Department of Neurology, The First People's Hospital of Jiangxia District) ;
  • Aofei Liu (Department of Medicine, Soochow University) ;
  • Ji Zhou (Department of Medicine, Soochow University) ;
  • Ting Yang (Department of Neurology, The First People's Hospital of Jiangxia District) ;
  • Yuanfeng Jiang (Department of Medicine, Soochow University) ;
  • Xia Li (Department of Medicine, Soochow University) ;
  • Weijian Jiang (Department of Medicine, Soochow University)
  • 투고 : 2023.10.05
  • 심사 : 2024.01.18
  • 발행 : 2024.05.01
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초록

Dexmedetomidine displays multiple mechanisms of neuroprotection in ameliorating ischemic brain injury. In this study, we explored the beneficial effects of dexmedetomidine on blood-brain barrier (BBB) integrity and neuroinflammation in cerebral ischemia/reperfusion injury. Sprague-Dawley rats were subjected to middle cerebral artery occlusion (MCAO) for 1.5 h and reperfusion for 24 h to establish a rat model of cerebral ischemia/reperfusion injury. Dexmedetomidine (9 ㎍/kg) was administered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 ㎍/kg) was injected intraperitoneally 30 min before MCAO. Brain damages were evaluated by 2,3,5-triphenyltetrazolium chloride staining, hematoxylin-eosin staining, Nissl staining, and brain water content assessment. BBB permeability was examined by Evans blue staining. Expression levels of claudin-5, zonula occludens-1, occludin, and matrix metalloproteinase-9 (MMP-9) as well as M1/M2 phenotypes-associated markers were assessed using immunofluorescence, RT-qPCR, Western blotting, and gelatin zymography. Enzyme-linked immunosorbent assay was used to examine inflammatory cytokine levels. We found that dexmedetomidine or SB203580 attenuated infarct volume, brain edema, BBB permeability, and neuroinflammation, and promoted M2 microglial polarization after cerebral ischemia/reperfusion injury. Increased MMP-9 activity by ischemia/reperfusion injury was inhibited by dexmedetomidine or SB203580. Dexmedetomidine inhibited the activation of the ERK, JNK, and p38 MAPK pathways. Moreover, activation of JNK or p38 MAPK reversed the protective effects of dexmedetomidine against ischemic brain injury. Overall, dexmedetomidine ameliorated brain injury by alleviating BBB permeability and promoting M2 polarization in experimental cerebral ischemia/reperfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

키워드

과제정보

This work was supported by The National Natural Science Foundation of China (No. 81471767, No.81871464).

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