Department of Neurosurgery, Liaocheng People's hospital, Liaocheng, China.
Department of Neurosurgery, Xuanwu Hospital, Capital Medical University, Beijing, China.
Front Immunol. 2022 Jul 4;13:917974. doi: 10.3389/fimmu.2022.917974. eCollection 2022.
BACKGROUND: Neuroinflammatory response contributes to early neurological deterioration (END) and unfavorable long-term functional outcome in patients with acute ischemic stroke (AIS) who recanalized successfully by endovascular thrombectomy (EVT), but there are no reliable biomarkers for their accurate prediction. Here, we sought to determine the temporal plasma profiles of the bioactive lipid mediators lipoxin A4 (LXA4), resolvin D1 (RvD1), and leukotriene B4 (LTB4) for their associations with clinical outcome. METHODS: We quantified levels of LXA4, RvD1, and LTB4 in blood samples retrospectively and longitudinally collected from consecutive AIS patients who underwent complete angiographic recanalization by EVT at admission (pre-EVT) and 24 hrs post-EVT. The primary outcome was unfavorable long-term functional outcome, defined as a 90-day modified Rankin Scale score of 3-6. Secondary outcome was END, defined as an increase in National Institutes of Health Stroke Scale (NIHSS) score ≥4 points at 24 hrs post-EVT. RESULTS: Eighty-one consecutive AIS patients and 20 healthy subjects were recruited for this study. Plasma levels of LXA4, RvD1, and LTB4 were significantly increased in post-EVT samples from AIS patients, as compared to those of healthy controls. END occurred in 17 (20.99%) patients, and 38 (46.91%) had unfavorable 90-day functional outcome. Multiple logistic regression analyses demonstrated that post-EVT levels of LXA4 (adjusted odd ratio [OR] 0.992, 95% confidence interval [CI] 0.987-0.998), ΔLXA4 (adjusted OR 0.995, 95% CI 0.991-0.999), LTB4 (adjusted OR 1.003, 95% CI 1.001-1.005), ΔLTB4 (adjusted OR 1.004, 95% CI 1.002-1.006), and post-EVT LXA4/LTB4 (adjusted OR 0.023, 95% CI 0.001-0.433) and RvD1/LTB4 (adjusted OR 0.196, 95% CI 0.057-0.682) ratios independently predicted END, and post-EVT LXA4 levels (adjusted OR 0.995, 95% CI 0.992-0.999), ΔLXA4 levels (adjusted OR 0.996, 95% CI 0.993-0.999), and post-EVT LXA4/LTB4 ratio (adjusted OR 0.285, 95% CI 0.096-0.845) independently predicted unfavorable 90-day functional outcome. These were validated using receiver operating characteristic curve analyses. CONCLUSIONS: Plasma lipid mediators measured 24 hrs post-EVT were independent predictors for early and long-term outcomes. Further studies are needed to determine their causal-effect relationship, and whether the imbalance between anti-inflammatory/pro-resolving and pro-inflammatory lipid mediators could be a potential adjunct therapeutic target.
背景：神经炎症反应有助于急性缺血性中风（AIS）患者在血管内血栓切除术（EVT）成功再通后出现早期神经功能恶化（END）和不良的长期功能结局，但目前尚无可靠的生物标志物可准确预测。在这里，我们试图确定生物活性脂质介质脂氧素 A4（LXA4）、分辨率 D1（RvD1）和白三烯 B4（LTB4）的时间血浆谱，以了解它们与临床结局的关系。
方法：我们回顾性地从连续接受 EVT 完全血管再通的 AIS 患者入院时（术前）和术后 24 小时（术后）的血液样本中定量检测 LXA4、RvD1 和 LTB4 的水平。主要结局为不良的长期功能结局，定义为 90 天时改良 Rankin 量表评分 3-6 分。次要结局为 END，定义为术后 24 小时 NIHSS 评分增加≥4 分。
结果：这项研究共纳入了 81 例连续的 AIS 患者和 20 名健康对照者。与健康对照组相比，术后 AIS 患者的 LXA4、RvD1 和 LTB4 血浆水平显著升高。17 例（20.99%）患者发生 END，38 例（46.91%）患者 90 天功能结局不良。多变量逻辑回归分析表明，术后 LXA4 水平（调整后的比值比 [OR]0.992，95%置信区间 [CI]0.987-0.998）、ΔLXA4（调整后的 OR 0.995，95%CI0.991-0.999）、LTB4（调整后的 OR 1.003，95%CI1.001-1.005）、ΔLTB4（调整后的 OR 1.004，95%CI1.002-1.006）、术后 LXA4/LTB4 比值（调整后的 OR 0.023，95%CI0.001-0.433）和 RvD1/LTB4 比值（调整后的 OR 0.196，95%CI0.057-0.682）独立预测 END，术后 LXA4 水平（调整后的 OR 0.995，95%CI0.992-0.999）、ΔLXA4 水平（调整后的 OR 0.996，95%CI0.993-0.999）和术后 LXA4/LTB4 比值（调整后的 OR 0.285，95%CI0.096-0.845）独立预测 90 天不良功能结局。这些结果通过接受者操作特征曲线分析得到了验证。
结论：术后 24 小时测量的血浆脂质介质是早期和长期结局的独立预测因子。需要进一步研究以确定它们的因果关系，以及抗炎/促分解和促炎脂质介质之间的失衡是否可以成为潜在的辅助治疗靶点。
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