Abstract
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.
Highlights
Subarachnoid hemorrhage (SAH) is a severe life-threatening acute cerebrovascular disease with a high rate of mortality and disability (Macdonald and Schweizer, 2017; Zhang et al, 2018)
We evaluated the role and explored the potential mechanisms of Resolvin D1 (RVD1) in early brain injury (EBI) after SAH
The results revealed that endogenous expression of RVD1 was decreased, whereas Formyl peptide receptor 2 (FPR2)
Summary
Subarachnoid hemorrhage (SAH) is a severe life-threatening acute cerebrovascular disease with a high rate of mortality and disability (Macdonald and Schweizer, 2017; Zhang et al, 2018). Increasing research suggests that early brain injury (EBI) occurring within 72 h of SAH is responsible for the disease prognosis The exact mechanism of EBI after SAH remains unclear, and there is a lack of effective therapeutic agents. Inflammation and blood-brain barrier (BBB) disruption are thought to contribute to EBI (Sehba et al, 2012; Suzuki, 2015).
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