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Resolvin D1 Attenuates Innate Immune Reactions in Experimental Subarachnoid Hemorrhage Rat Model
Molecular Neurobiology ( IF 4.6 ) Pub Date : 2021-01-07 , DOI: 10.1007/s12035-020-02237-1
Guang-Jie Liu 1 , Tao Tao 2 , Xiang-Sheng Zhang 1 , Yue Lu 1 , Ling-Yun Wu 1 , Yong-Yue Gao 1 , Han Wang 3 , Hai-Bin Dai 1 , Yan Zhou 1 , Zong Zhuang 1 , Chun-Hua Hang 1 , Wei Li 1
Affiliation  

Excessive inflammation is a major cause contributing to early brain injury (EBI) and is associated with negative or catastrophic outcomes of subarachnoid hemorrhage (SAH). Resolvin D1 (RvD1) exerts strong anti-inflammatory and pro-resolving effects on either acute or chronic inflammation of various origin. Henceforth, we hypothesized that RvD1 potentially attenuates excessive inflammation in EBI following SAH. Therefore, we generated a filament perforation SAH model and administered 3 different doses (0.3, 0.6, and 1.2 nmol) of RvD1 after experimental SAH. Neurological scores, brain edema, and blood–brain barrier integrity were evaluated; besides, neutrophil infiltration, neuronal deaths, and microglial pro-inflammatory polarization were observed using histopathology or immunofluorescence staining, western blots, and qPCR. After confirming the effectiveness of RvD1 in SAH, we administered the FPR2-specific antagonist Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4) 30 min before SAH establishment to observe whether this compound could abolish the anti-inflammatory effect of RvD1. Altogether, our results showed that RvD1 exerted a strong anti-inflammatory effect and markedly reduced neutrophil infiltration and microglial pro-inflammatory activation, leading to remarkable improvements in neurological function and brain tissue restoration. After addition of WRW4, the anti-inflammatory effects of RvD1 were abolished. These results indicated that RvD1 could exert a good anti-inflammatory effect and alleviate EBI, which suggested that RvD1 might be a novel therapeutic alternative for SAH-induced injury.



中文翻译:

Resolvin D1 减弱实验性蛛网膜下腔出血大鼠模型中的先天免疫反应

过度炎症是导致早期脑损伤 (EBI) 的主要原因,并且与蛛网膜下腔出血 (SAH) 的负面或灾难性结果相关。Resolvin D1 (RvD1) 对各种来源的急性或慢性炎症具有很强的抗炎和促消退作用。此后,我们假设 RvD1 可能会减轻 SAH 后 EBI 中的过度炎症。因此,我们生成了一个细丝穿孔 SAH 模型,并在实验性 SAH 后给予了 3 种不同剂量(0.3、0.6 和 1.2 nmol)的 RvD1。评估了神经系统评分、脑水肿和血脑屏障完整性;此外,使用组织病理学或免疫荧光染色、蛋白质印迹和 qPCR 观察到中性粒细胞浸润、神经元死亡和小胶质细胞促炎极化。在确认 RvD1 在 SAH 中的有效性后,我们在 SAH 建立前 30 分钟给予 FPR2 特异性拮抗剂 Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4),以观察该化合物是否可以消除RVD1。总之,我们的结果表明,RvD1 具有很强的抗炎作用,显着减少中性粒细胞浸润和小胶质细胞促炎激活,显着改善神经功能和脑组织恢复。添加 WRW4 后,RvD1 的抗炎作用被取消。这些结果表明 RvD1 可以发挥良好的抗炎作用并减轻 EBI,这表明 RvD1 可能是 SAH 诱导的损伤的新治疗替代方案。我们在 SAH 建立前 30 分钟给予 FPR2 特异性拮抗剂 Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4),以观察该化合物是否可以消除 RvD1 的抗炎作用。总之,我们的结果表明,RvD1 具有很强的抗炎作用,显着减少中性粒细胞浸润和小胶质细胞促炎激活,显着改善神经功能和脑组织恢复。添加 WRW4 后,RvD1 的抗炎作用被取消。这些结果表明 RvD1 可以发挥良好的抗炎作用并减轻 EBI,这表明 RvD1 可能是 SAH 诱导的损伤的新治疗替代方案。我们在 SAH 建立前 30 分钟给予 FPR2 特异性拮抗剂 Trp-Arg-Trp-Trp-Trp-Trp-NH2 (WRW4),以观察该化合物是否可以消除 RvD1 的抗炎作用。总之,我们的结果表明,RvD1 具有很强的抗炎作用,显着减少中性粒细胞浸润和小胶质细胞促炎激活,显着改善神经功能和脑组织恢复。添加 WRW4 后,RvD1 的抗炎作用被取消。这些结果表明 RvD1 可以发挥良好的抗炎作用并减轻 EBI,这表明 RvD1 可能是 SAH 诱导的损伤的新治疗替代方案。

更新日期:2021-01-07
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