Faculty of Health and Medical Sciences, Department of Neuroscience, University of Copenhagen, Blegdamsvej 3, DK-2200, Copenhagen N, Denmark.
Department of Neuroanaesthesiology, The Neuroscience Center, Copenhagen University Hospital-Rigshospitalet, Copenhagen, Denmark.
Fluids Barriers CNS. 2023 Jun 23;20(1):49. doi: 10.1186/s12987-023-00451-2.
It is crucial to maintain the intracranial pressure (ICP) within the physiological range to ensure proper brain function. The ICP may fluctuate during the light-dark phase cycle, complicating diagnosis and treatment choice in patients with pressure-related disorders. Such ICP fluctuations may originate in circadian or sleep-wake cycle-mediated modulation of cerebrospinal fluid (CSF) flow dynamics, which in addition could support diurnal regulation of brain waste clearance.
ICP was monitored continuously in patients who underwent placement of an external ventricular drain (EVD) and by telemetric monitoring in experimental rats. CSF was collected via the EVD in patients and the rodent CSF secretion rate determined by in vivo experimentation. Rodent choroid plexus transporter transcripts were quantified with RNAseq and transport activity with ex vivo isotope transport assays.
We demonstrated that ICP increases by 30% in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients (12%) and CSF production rate in rats (20%), the latter obtained with the ventriculo-cisternal perfusion assay. The dark-phase increase in CSF secretion in rats was, in part, assigned to increased transport activity of the choroid plexus Na,K,2Cl cotransporter (NKCC1), which is implicated in CSF secretion by this tissue.
CSF secretion, and thus ICP, increases in the dark phase in humans and rats, irrespective of their diurnal/nocturnal activity preference, in part due to altered choroid plexus transport activity in the rat. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself.
维持颅内压（ICP）在生理范围内对于确保大脑功能正常至关重要。ICP 在光-暗周期循环中可能会发生波动，这使得与压力相关的疾病患者的诊断和治疗选择变得复杂。这种 ICP 波动可能起源于脑脊液（CSF）流动动力学的昼夜节律或睡眠-觉醒周期介导的调节，此外，它还可以支持大脑废物清除的昼夜调节。
我们在接受外部脑室引流（EVD）放置的患者中连续监测 ICP，并在实验大鼠中通过遥测监测 ICP。通过 EVD 在患者中收集 CSF，并通过体内实验确定大鼠 CSF 分泌率。使用 RNAseq 定量啮齿动物脉络丛转运体转录本，并使用离体同位素转运测定法测定转运活性。
我们证明，在两种物种中，ICP 在暗期增加了 30%，这与血管参数无关。这种增加与患者 CSF 采集量增加（12%）和大鼠 CSF 产生率增加（20%）相吻合，后者通过脑室-蛛网膜下腔灌流测定获得。大鼠 CSF 分泌在暗期的增加部分归因于脉络丛 Na，K，2Cl 共转运体（NKCC1）的转运活性增加，该转运体参与了该组织的 CSF 分泌。
无论人类和大鼠的昼夜/夜间活动偏好如何，CSF 分泌，从而 ICP 在暗期都会增加，这部分归因于大鼠脉络丛转运活性的改变。我们的研究结果表明，CSF 动力学受昼夜节律调节，而不仅仅是睡眠本身。
