Resolvin D1 ameliorates Inflammation-Mediated Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in rats by Modulating A20 and NLRP3 Inflammasome

Chengcong Wei; Chengcong Wei; Shenquan Guo; Wenchao Liu; Fa Jin; Boyang Wei; Haiyan Fan; Hengxian Su; Jiahui Liu; Nan Zhang; Dazhao Fang; Guangxu Li; Shixing Shu; Xifeng Li; Xuying He; Xin Zhang; Chuanzhi Duan

doi:10.3389/fphar.2020.610734

Frontiers in Pharmacology (Feb 2021)

Resolvin D1 ameliorates Inflammation-Mediated Blood-Brain Barrier Disruption After Subarachnoid Hemorrhage in rats by Modulating A20 and NLRP3 Inflammasome

Chengcong Wei,
Chengcong Wei,
Shenquan Guo,
Wenchao Liu,
Fa Jin,
Boyang Wei,
Haiyan Fan,
Hengxian Su,
Jiahui Liu,
Nan Zhang,
Dazhao Fang,
Guangxu Li,
Shixing Shu,
Xifeng Li,
Xuying He,
Xin Zhang,
Chuanzhi Duan

Affiliations

Chengcong Wei: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Chengcong Wei: Department of Neurosurgery, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, China
Shenquan Guo: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Wenchao Liu: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Fa Jin: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Boyang Wei: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Haiyan Fan: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Hengxian Su: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Jiahui Liu: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Nan Zhang: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Dazhao Fang: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Guangxu Li: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Shixing Shu: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Xifeng Li: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Xuying He: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Xin Zhang: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China
Chuanzhi Duan: Neurosurgery Center, Department of Cerebrovascular Surgery, The National Key Clinical Specialty, Engineering Technology Research Center of Education Ministry of China on Diagnosis and Treatment of Cerebrovascular Disease, Guangdong Provincial Key Laboratory on Brain Function Repair and Regeneration, The Neurosurgery Institute of Guangdong Province, Zhujiang Hospital, Southern Medical University, Guangzhou, China

DOI: https://doi.org/10.3389/fphar.2020.610734
Journal volume & issue: Vol. 11

Abstract

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Inflammation is typically related to dysfunction of the blood-brain barrier (BBB) that leads to early brain injury (EBI) after subarachnoid hemorrhage (SAH). Resolvin D1 (RVD1), a lipid mediator derived from docosahexaenoic acid, possesses anti-inflammatory and neuroprotective properties. This study investigated the effects and mechanisms of RVD1 in SAH. A Sprague-Dawley rat model of SAH was established through endovascular perforation. RVD1was injected through the femoral vein at 1 and 12 h after SAH induction. To further explore the potential neuroprotective mechanism, a formyl peptide receptor two antagonist (WRW4) was intracerebroventricularly administered 1 h after SAH induction. The expression of endogenous RVD1 was decreased whereas A20 and NLRP3 levels were increased after SAH. An exogenous RVD1 administration increased RVD1 concentration in brain tissue, and improved neurological function, neuroinflammation, BBB disruption, and brain edema. RVD1 treatment upregulated the expression of A20, occludin, claudin-5, and zona occludens-1, as well as downregulated nuclear factor-κBp65, NLRP3, matrix metallopeptidase 9, and intercellular cell adhesion molecule-1 expression. Furthermore, RVD1 inhibited microglial activation and neutrophil infiltration and promoted neutrophil apoptosis. However, the neuroprotective effects of RVD1 were abolished by WRW4. In summary, our findings reveal that RVD1 provides beneficial effects against inflammation-triggered BBB dysfunction after SAH by modulating A20 and NLRP3 inflammasome.

Published in Frontiers in Pharmacology

ISSN: 1663-9812 (Online)
Publisher: Frontiers Media S.A.
Country of publisher: Switzerland
LCC subjects: Medicine: Therapeutics. Pharmacology
Website: http://journal.frontiersin.org/journals/pharmacology

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