Resolvins, a new family from the endogenous specialized pro-resolving mediators (SPMs), promote the resolution of the inflammatory response. Resolvin D3 (RvD3), a docosahexaenoic acid (DHA) product, has been known to suppress the inflammatory response. However, the anti-inflammatory and neuroprotective effects of RvD3 are not known in a model of spinal cord injury (SCI). Here, we investigated the anti-inflammatory and neuroprotective effect of RvD3 in a mouse model of SCI. Processes associated with anti-inflammation and angiogenesis were studied in RAW 264.7 cells and the human brain endothelial cell line hCMEC/D3, respectively. Additionally, female C57BL/6 mice were subjected to moderate compression SCI (20-g weight compression for 1 min) followed by intrathecal injection of vehicle or RvD3 (1 μg/20 μL) at 1 h post-SCI. RvD3 decreased the lipopolysaccharide (LPS)-induced production of inflammatory mediators and nitric oxide (NO) in RAW 264.7 cells and promoted an angiogenic effect in the hCMEC/D3 cell line. Treatment with RvD3 improved locomotor recovery and reduced thermal hyperalgesia in SCI mice compared with vehicle treatment at 14 days post-SCI. Remarkably, RvD3-treated mice exhibited reduced expression of inflammatory cytokines (TNF-α, IL6, IL1β) and chemokines (CCL2, CCL3). Also, RvD3-treated mice exhibited increased expression of tight junction proteins such as zonula occludens (ZO)-1 and occludin. Furthermore, immunohistochemistry showed a decreased level of gliosis (GFAP, Iba-1) and neuroinflammation (CD68, TGF-β) and enhanced neuroprotection. These data provide evidence that intrathecal injection of RvD3 represents a promising therapeutic strategy to promote inflammatory resolution, neuroprotection, and neurological functional recovery following SCI.

中文翻译：

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Resolvin D3 促进脊髓损伤后的炎症消退、神经保护和功能恢复。

Resolvins 是一种来自内源性特化促消解介质 (SPM) 的新家族，可促进炎症反应的消退。Resolvin D3 (RvD3) 是一种二十二碳六烯酸 (DHA) 产品，已知可抑制炎症反应。然而，在脊髓损伤 (SCI) 模型中，RvD3 的抗炎和神经保护作用尚不清楚。在这里，我们研究了 RvD3 在 SCI 小鼠模型中的抗炎和神经保护作用。分别在 RAW 264.7 细胞和人脑内皮细胞系 hCMEC/D3 中研究了与抗炎和血管生成相关的过程。此外，对雌性 C57BL/6 小鼠进行适度压缩 SCI（20 克重量压缩 1 分钟），然后在 SCI 后 1 小时鞘内注射载体或 RvD3（1 微克/20 微升）。RvD3 减少了脂多糖 (LPS) 诱导的 RAW 264.7 细胞炎症介质和一氧化氮 (NO) 的产生，并促进了 hCMEC/D3 细胞系的血管生成作用。与 SCI 后 14 天的载体治疗相比，用 RvD3 治疗改善了 SCI 小鼠的运动恢复并减少了热痛觉过敏。值得注意的是，RvD3 治疗的小鼠表现出炎性细胞因子（TNF-α、IL6、IL1β）和趋化因子（CCL2、CCL3）的表达降低。此外，RvD3 处理的小鼠表现出增加的紧密连接蛋白的表达，例如封闭小带 (ZO)-1 和 occludin。此外，免疫组织化学显示神经胶质增生（GFAP、Iba-1）和神经炎症（CD68、TGF-β）水平降低，神经保护作用增强。