Retinal and Cortical Blood Flow Dynamics Following Systemic Blood-Neural Barrier Disruption
Retinal and Cortical Blood Flow Dynamics Following Systemic Blood-Neural Barrier Disruption
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DOI：
10.3389/fnins.2017.00568
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发表时间：
2017-10-12
影响因子：
4.3
通讯作者：
Bui, Bang V.
中科院分区：
文献类型：
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作者：
Hui, Flora;Nguyen, Christine T. O.;Bui, Bang V.
为了考虑视网膜脉管系统成像是否可以用作皮质血管的标记，我们比较了药物破坏血液神经屏障之前和之后的荧光素血管造影血流动力学。将荧光素钠（1%，200μl/kg）静脉内递送至麻醉的成年Long Evans大鼠（n=44，脑=18，视网膜=26）。在大脑队列中，创建了一个颅窗，以便直接观察表面皮质血管。使用啮齿动物视网膜摄像机以 30 帧/秒的速度捕获视频荧光素血管造影，并评估达到 50% 亮度（半上升）、50% 衰减（半下降）的时间和残余荧光的平台水平（偏移，%）的荧光强度分布。与视网膜脉管系统相比，皮质血管发出荧光的时间更早（动脉半上升：5.6 +/- 0.2 秒），并且衰减得更快（半下降：10.3 +/- 0.2 秒）。皮质血管也有相当高的偏移，特别是在毛细血管/血管外空间（41.4 +/- 2.7%），而视网膜中的色素减少了这种残留荧光。在一组动物中，静脉注射脱氧胆酸钠（DOC，0.06M 溶解在无菌盐水中，1mL），同时破坏血脑屏障和血视网膜屏障。另一组接受盐水作为载体对照。在药物输注后 6 小时和 24 小时重新测量荧光素血管造影，并通过将血流动力学与对照组的上四分位数（75%）进行比较来进行评估。视网膜脉管系统对 DOC 诱导的破坏更敏感，6 小时时荧光偏移更高 (47.3 +/- 10.6%)。在皮质血管中观察到延迟效应，仅在 24 小时时出现较高的偏移（65.6 +/- 10.1%）。在这里，我们开发了一种定量比较视网膜和浅层皮质血管中荧光素血管造影动力学的方法。我们的结果表明，血液神经屏障的系统性破坏会导致两种组织中的血管渗漏，但在视网膜中更早出现，这表明药理学血液神经屏障破坏可能在眼睛中比在皮质脉管系统中更早被检测到。
To consider whether imaging retinal vasculature may be used as a marker for cortical vessels, we compared fluorescein angiography flow dynamics before and after pharmacological disruption of blood-neural barriers. Sodium fluorescein (1%, 200 mu l/kg) was intravenously delivered in anesthetized adult Long Evans rats (n = 44, brain = 18, retina = 26). In the brain cohort, a cranial window was created to allow direct visualization of surface cortical vessels. Video fluorescein angiography was captured using a rodent retinal camera at 30 frames/second and fluorescence intensity profiles were evaluated for the time to reach 50% brightness (half-rise), 50% decay (half-fall), and the plateau level of remnant fluorescence (offset, %). Cortical vessels fluoresced earlier (artery half-rise: 5.6 +/- 0.2 s) and decayed faster (half-fall: 10.3 +/- 0.2 s) compared to retinal vasculature. Cortical vessels also had a considerably higher offset, particularly in the capillaries/extravascular space (41.4 +/- 2.7%) whereas pigment in the retina reduces such residual fluorescence. In a sub-cohort of animals, sodium deoxycholate (DOC, 0.06M dissolved in sterile saline, 1mL) was delivered intravenously to cause simultaneous disruption of the blood-brain and blood-retinal barriers. A separate group received saline as vehicle control. Fluorescein angiography was re-measured at 6 and 24 h after drug infusion and evaluated by comparing flow dynamics to the upper quartile (75%) of the control group. Retinal vasculature was more sensitive to DOC-induced disruption with a higher fluorescence offset at 6 h (47.3 +/- 10.6%). A delayed effect was seen in cortical vessels with a higher offset evident only at 24 h (65.6 +/- 10.1%). Here we have developed a method to quantitatively compare fluorescein angiography dynamics in the retina and superficial cortical vessels. Our results show that systemic disruption of blood-neural barriers causes vascular leakage in both tissues but earlier in the retina suggesting that pharmacological blood-neural barrier disruption may be detected earlier in the eye than in cortical vasculature.