Dexmedetomidine alleviates blood-brain barrier disruption in rats after cerebral ischemia-reperfusion by suppressing JNK and p38 MAPK signaling

• 발행기관: 대한생리학회-대한약리학회
• 저자명: Canmin Zhu Dili Wang Chang Chang Aofei Liu Ji Zhou Ting Yang Yuanfeng Jiang Xia Li Weijian Jiang
• 간행물 정보: 『The Korean Journal of Physiology & Pharmacology』제28권 제3호, 239~252쪽, 전체 14쪽
• 주제분류: 의약학 > 의학일반
• 파일형태: PDF
• 발행일자: 2024.05.01

국문 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 􀀁g/kg) was ad-ministered to rats 30 min after MCAO through intravenous injection, and SB203580 (a p38 MAPK inhibitor, 200 􀀁g/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 dexme-detomidine 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 in-jury 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/re-perfusion injury model by inhibiting the activation of JNK and p38 MAPK pathways.

목차

INTRODUCTION

METHODS

RESULTS

DISCUSSION

키워드

Blood-brain barrier Dexmedetomidine Matrix metalloproteinase 9 Microglia Middle cerebral artery occlusion p38 mitogen-activated protein kinases