Nocturnal increase in cerebrospinal fluid secretion as a regulator of intracranial pressure

Abstract

ABSTRACTIt 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. Through a combination of patient data andin vivotelemetric pressure measurements in adult male rats, we demonstrated that ICP increases in the dark phase in both species, independently of vascular parameters. This increase aligns with elevated CSF collection in patients and CSF production rate in rats, 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. In conclusion, 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. Our findings suggest that CSF dynamics are modulated by the circadian rhythm, rather than merely sleep itself.