Wei Chengcong, Guo Shenquan, Liu Wenchao, Jin Fa, Wei Boyang, Fan Haiyan, Su Hengxian, Liu Jiahui, Zhang Nan, Fang Dazhao, Li Guangxu, Shu Shixing, Li Xifeng, He Xuying, Zhang Xin, Duan Chuanzhi
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.
Department of Neurosurgery, Minzu Hospital of Guangxi Zhuang Autonomous Region, Affiliated Minzu Hospital of Guangxi Medical University, Nanning, China.
Front Pharmacol. 2021 Feb 3;11:610734. doi: 10.3389/fphar.2020.610734. eCollection 2020.
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.
炎症通常与血脑屏障（BBB）功能障碍有关，血脑屏障功能障碍会导致蛛网膜下腔出血（SAH）后的早期脑损伤（EBI）。消退素D1（RVD1）是一种源自二十二碳六烯酸的脂质介质，具有抗炎和神经保护特性。本研究调查了RVD1在SAH中的作用及机制。通过血管内穿刺建立SAH的Sprague-Dawley大鼠模型。在SAH诱导后1小时和12小时通过股静脉注射RVD1。为了进一步探索潜在的神经保护机制，在SAH诱导后1小时脑室内注射甲酰肽受体2拮抗剂（WRW4）。SAH后内源性RVD1表达降低，而A20和NLRP3水平升高。外源性给予RVD1可增加脑组织中RVD1浓度，并改善神经功能、神经炎症、血脑屏障破坏和脑水肿。RVD1治疗上调了A20、闭合蛋白、claudin-5和紧密连接蛋白1的表达，同时下调了核因子-κBp65、NLRP3、基质金属蛋白酶9和细胞间黏附分子1的表达。此外，RVD1抑制小胶质细胞活化和中性粒细胞浸润，并促进中性粒细胞凋亡。然而，WRW4消除了RVD1的神经保护作用。总之，我们的研究结果表明，RVD1通过调节A20和NLRP3炎性小体，对SAH后炎症引发的血脑屏障功能障碍具有有益作用。
