Growing evidence indicates that perivascular tissue is critical to modulate vessel function. We hypothesized that the arachnoid membrane surrounding middle cerebral artery (MCA) regulates its function via sphingosine-1-phosphate (S1P)-induced vasoconstriction. The MCA from 3- to 9-month-old male and female wild-type (Oncine France 1 and C57BL/6) mice and sphingosine kinase 2 knockout (SphK2-/-) mice in the C57BL/6 background was mounted in pressure myographs with and without arachnoid membrane. Raman microspectroscopy and imaging were used for in situ detection of S1P. The presence of arachnoid tissue was associated with reduced external and lumen MCA diameters, and with an increase in basal tone regardless of sex and strain background. Strong S1P-positive signals were detected in the arachnoid surrounding the MCA wall in both mice models, as well as in a human post-mortem specimen. Selective S1P receptor 3 antagonist TY 52156 markedly reduced both MCA vasoconstriction induced by exogenous S1P and arachnoid-dependent basal tone increase. Compared to 3-month-old mice, the arachnoid-mediated contractile influence persisted in 9-month-old mice despite a decline in arachnoid S1P deposits. Genetic deletion of SphK2 decreased arachnoid S1P content and vasoconstriction. This is the first experimental evidence that arachnoid membrane regulates the MCA tone mediated by S1P.

越来越多的证据表明血管周围组织对调节血管功能至关重要。我们假设大脑中动脉 (MCA) 周围的蛛网膜通过 1-磷酸鞘氨醇 (S1P) 诱导的血管收缩来调节其功能。将 C57BL/6 背景中 3 至 9 个月大的雄性和雌性野生型（Oncine France 1 和 C57BL/6）小鼠和鞘氨醇激酶 2 敲除 (SphK2-/-) 小鼠的 MCA 安装在压力肌动描记图中有无蛛网膜。拉曼显微光谱和成像用于 S1P 的原位检测。蛛网膜组织的存在与减少的外部和管腔 MCA 直径有关，并且无论性别和应变背景如何，都与基底张力的增加有关。在两种小鼠模型中，在 MCA 壁周围的蛛网膜中检测到强烈的 S1P 阳性信号，以及在人类死后标本中。选择性 S1P 受体 3 拮抗剂 TY 52156 显着降低外源性 S1P 诱导的 MCA 血管收缩和蛛网膜依赖性基础张力增加。与 3 个月大的小鼠相比，蛛网膜介导的收缩影响在 9 个月大的小鼠中持续存在，尽管蛛网膜 S1P 沉积物有所下降。SphK2 的遗传缺失降低了蛛网膜 S1P 含量和血管收缩。这是蛛网膜调节由 S1P 介导的 MCA 音调的第一个实验证据。尽管蛛网膜 S1P 沉积物减少，但 9 个月大的小鼠中蛛网膜介导的收缩影响仍然存在。SphK2 的遗传缺失降低了蛛网膜 S1P 含量和血管收缩。这是蛛网膜调节由 S1P 介导的 MCA 音调的第一个实验证据。尽管蛛网膜 S1P 沉积物减少，但 9 个月大的小鼠中蛛网膜介导的收缩影响仍然存在。SphK2 的遗传缺失降低了蛛网膜 S1P 含量和血管收缩。这是蛛网膜调节由 S1P 介导的 MCA 音调的第一个实验证据。