There is thought to be a strong relationship between sphingosine-1-phosphate (S1P) signaling and pathophysiolosy of cerebral ischemia. We examined the change of expression and distribution of S1P receptors (S1PRs) and sphingosine kinases (SphKs) after cerebral ischemia in male C57BL6/J mice using immunohistochemical analysis at 1, 5, 14, and 28 days after 30 min of transient middle cerebral artery occlusion (tMCAO). S1PR1, 3, and 5 were transiently induced in the cells, which were morphologically similar to neurons in the peri-infarct lesion with a peak seen at 1 day after tMCAO (p < 0.01 vs. sham control). S1PR2 appeared in the inner layer of vessels in the ischemic core (p < 0.01 vs. sham control) and the peri-infarct lesion (p < 0.01 vs. sham control) at the acute phase after tMCAO. However, SphK1 was strongly induced at 1 and 5 days after tMCAO (p < 0.01 vs. sham control) in the peri-infarct lesion, whereas SphK2 expression did not change. Western blot analysis at 1 and 5 days after 30 min of tMCAO revealed that the expression of S1PRs were transiently enhanced at the acute phase, which was consistent with the immunohistochemical results. Double immunofluorescent analysis revealed S1PR2/NG2- and S1PR2/CD31-, S1PR3/CD31-, and S1PR5/CD31-double positive cells in the peri-infarct lesion 1 day after tMCAO. The present results suggest that S1PRs and SphK1 may be important therapeutic targets for rescuing the peri-infarct lesion.

中文翻译：

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小鼠暂时性大脑中动脉闭塞后缺血周围区域鞘氨醇 1-磷酸受体和鞘氨醇激酶 1 的上调。

人们认为 1-磷酸鞘氨醇 (S1P) 信号传导与脑缺血的病理生理学之间存在密切关系。我们在短暂大脑中动脉 30 分钟后的 1、5、14 和 28 天使用免疫组织化学分析检查了雄性 C57BL6/J 小鼠脑缺血后 S1P 受体 (S1PRs) 和鞘氨醇激酶 (SphKs) 的表达和分布的变化闭塞（tMCAO）。S1PR1、3 和 5 在细胞中被瞬时诱导，在形态学上与梗塞周围病变中的神经元相似，在 tMCAO 后 1 天出现峰值（p < 0.01 与假对照）。在 tMCAO 后的急性期，S1PR2 出现在缺血核心（p < 0.01 与假对照）和梗塞周围病变（p < 0.01 与假对照）的血管内层中。然而，SphK1 在 tMCAO 后 1 天和 5 天被强烈诱导（p < 0.01 与假对照）在梗塞周围病变中，而 SphK2 表达没有变化。tMCAO 30 分钟后第 1 天和第 5 天的蛋白质印迹分析显示，S1PRs 的表达在急性期瞬时增强，这与免疫组化结果一致。双免疫荧光分析显示 tMCAO 后 1 天梗塞周围病变中出现 S1PR2/NG2-和 S1PR2/CD31-、S1PR3/CD31-和 S1PR5/CD31-双阳性细胞。目前的结果表明，S1PRs 和 SphK1 可能是挽救梗死周围病变的重要治疗靶点。tMCAO 30 分钟后第 1 天和第 5 天的蛋白质印迹分析显示，S1PRs 的表达在急性期瞬时增强，这与免疫组化结果一致。双免疫荧光分析显示 tMCAO 后 1 天梗塞周围病变中出现 S1PR2/NG2-和 S1PR2/CD31-、S1PR3/CD31-和 S1PR5/CD31-双阳性细胞。目前的结果表明，S1PRs 和 SphK1 可能是挽救梗死周围病变的重要治疗靶点。tMCAO 30 分钟后第 1 天和第 5 天的蛋白质印迹分析显示，S1PRs 的表达在急性期瞬时增强，这与免疫组化结果一致。双免疫荧光分析显示 tMCAO 后 1 天梗塞周围病变中出现 S1PR2/NG2-和 S1PR2/CD31-、S1PR3/CD31-和 S1PR5/CD31-双阳性细胞。目前的结果表明，S1PRs 和 SphK1 可能是挽救梗死周围病变的重要治疗靶点。