Leukotriene B₄ (LTB₄) has been implicated in ischemic stroke pathology. We examined the prognostic significance of LTB₄ levels in patients with acute middle cerebral artery (MCA) infarction and their mechanisms in rat stroke models. In ischemic stroke patients with middle cerebral artery infarction, plasma LTB₄ levels were found to increase rapidly, roughly doubling within 24 h when compared to initial post-stroke levels. Further analyses indicate that poor functional recovery is associated with early and more sustained increase in LTB₄ rather than the peak levels. Results from studies using a rat embolic stroke model showed increased 5-lipoxygenase (5-LOX) expression in the ipsilateral infarcted cortex compared with sham control or respective contralateral regions at 24 h post-stroke with a concomitant increase in LTB₄ levels. In addition, neutrophil influx was also observed in the infarcted cortex. Double immunostaining indicated that neutrophils express 5-LOX and leukotriene A₄ hydrolase (LTA₄H), highlighting the pivotal contributions of neutrophils as a source of LTB₄. Importantly, rise in plasma LTB₄ levels corresponded with an increase in LTB₄ amount in the infarcted cortex, thereby supporting the use of plasma as a surrogate for brain LTB₄ levels. Pre-stroke LTB₄ loading increased brain infarct volume in tMCAO rats. Conversely, administration of the 5-LOX-activating protein (FLAP) inhibitor BAY-X1005 or B-leukotriene receptor (BLTR) antagonist LY255283 decreased the infarct volume by a similar extent. To conclude, targeted interruption of the LTB₄ pathway might be a viable treatment strategy for acute ischemic stroke.

中文翻译：

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白三烯 B4 水平的早期和持续升高与缺血性中风患者的不良临床结果有关。

白三烯 B ₄ (LTB ₄ ) 与缺血性中风病理学有关。我们检查了急性大脑中动脉 (MCA) 梗死患者LTB _{4水平的预后意义及其在大鼠卒中模型中的机制。}在伴有大脑中动脉梗塞的缺血性卒中患者中，血浆 LTB ₄水平迅速升高，与卒中后初始水平相比，在 24 小时内大约翻了一番。进一步的分析表明，功能恢复不佳与 LTB _{4的早期和更持续增加有关}而不是峰值水平。使用大鼠栓塞中风模型的研究结果显示，与假手术对照组或中风后 24 小时相应的对侧区域相比，同侧梗塞皮层中的 5-脂氧合酶 (5-LOX) 表达增加，同时 LTB ₄水平增加。此外，在梗塞的皮质中也观察到中性粒细胞流入。双免疫染色表明中性粒细胞表达 5-LOX 和白三烯 A ₄水解酶 (LTA ₄ H)，突出了中性粒细胞作为 LTB ₄来源的关键贡献。重要的是，血浆 LTB ₄水平的升高与LTB _{4的升高相对应}量，从而支持使用血浆作为脑 LTB ₄水平的替代物。中风前 LTB ₄负荷增加了 tMCAO 大鼠的脑梗死体积。相反，给予 5-LOX 激活蛋白 (FLAP) 抑制剂 BAY-X1005 或 B-白三烯受体 (BLTR) 拮抗剂 LY255283 可将梗塞体积减少相似程度。总而言之，靶向阻断 LTB ₄通路可能是急性缺血性卒中可行的治疗策略。