Reply to "A Letter Concerning a Role for Blood-Brain Barrier Dysfunction in Delirium following Noncardiac Surgery in Older Adults".
Reply to "A Letter Concerning a Role for Blood-Brain Barrier Dysfunction in Delirium following Noncardiac Surgery in Older Adults".
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回复“关于老年人非心脏手术后血脑屏障功能障碍在谵妄中的作用的一封信”。
DOI：
10.1002/ana.26834
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发表时间：
2024
影响因子：
11.2
通讯作者：
Berger,Miles
中科院分区：
文献类型：
--
作者：
Devinney,MichaelJ;Berger,Miles
我们一致认为，脑脊液与血浆白蛋白比率（CPAR）是血脑屏障（BBB）功能障碍的一个不完善的标志物，尽管它是最广泛接受的整体血脑屏障完整性/功能的分子生物标志物。 2, 3 事实上，很少有人类生物分子标记物（包括 CPAR）能够区分血脑脊液屏障 (BCSFB) 和 BBB 通透性。 BBB 和 BCSFB 是两个解剖学上不同的中枢神经系统屏障：BBB 位于脑微血管内的内皮细胞水平，而脉络丛的室管膜细胞形成 BCSFB。为了区分 BCSFB 和 BBB 通透性，需要使用神经成像 4 或死后脑组织免疫染色进行直接屏障检查。 5 尽管这些免疫染色技术不可能在活体患者中使用，但啮齿动物外科研究发现术后脑内水通道蛋白 4 和血管标志物（即 CD31）减少，并且右旋糖酐扩散到大脑中增加，这两者都表明术后 BBB 通透性增加。 6, 7 在一项针对老年心脏手术患者的小型研究中，通过“k-trans”MRI 测量的钆流入大脑的流出率在术后 24 小时增加，表明这种术后 BBB 功能障碍发生在人类身上。 8 因此，虽然我们没有直接研究 BBB（例如通过免疫染色或神经影像学），但上述研究表明，我们在老年手术患者中观察到的术后 CPAR 增加是（至少部分）归因于术后 BBB 功能障碍。尽管如此，我们同意，正式区分手术后 BBB 与 BCSFB 通透性变化是未来研究老年人谵妄和围手术期神经认知障碍的一个重要问题。
We agree that cerebrospinal fluid-to-plasma albumin ratio (CPAR) is an imperfect marker for blood-brain barrier (BBB) dysfunction, though it is the most widely accepted molecular biomarker for overall blood-brain barrier integrity/function. 2, 3 Indeed, few if any human biomolecular markers (including CPAR) distinguish between blood-cerebrospinal fluid barrier (BCSFB) and BBB permeability. The BBB and BCSFB are two anatomically distinct central nervous system barriers: the BBB is located at the level of endothelial cells within brain microvessels, while the ependymal cells of the choroid plexus form the BCSFB. To distinguish between BCSFB and BBB permeability, direct barrier examination using neuroimaging4 or post-mortem brain tissue immunostaining is required. 5 Although these immunostaining techniques are not possible to use in living patients, rodent surgical studies have found postoperative decreases in brain aquaporin-4 and vascular markers (ie, CD31) and increases in dextran diffusion into the brain, both of which suggest increased postoperative BBB permeability. 6, 7 In a small study of older cardiac surgery patients, the efflux rate of gadolinium into the brain measured with “k-trans” MRI was increased 24-hours postoperatively, suggesting that this postoperative BBB dysfunction occurs in humans. 8 Thus, although we did not study the BBB directly (such as via immunostaining or neuroimaging), the studies mentioned above suggest that the postoperative CPAR increases we observed in older surgical patients were due (at least in part) to postoperative BBB dysfunction. Nonetheless, we agree that formally differentiating between BBB vs BCSFB permeability changes following surgery is an important question for future studies on delirium and perioperative neurocognitive disorders in older adults.