Biology subjects

Steffensen, A. B.

Publications and source records attributed to Steffensen, A. B..

2 recordsLinked to original sources

bioRxiv2023

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

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. Through a combination of patient data and in vivo telemetric 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.

neuroscience↗

bioRxiv2021

Cerebrospinal fluid formation is controlled by membrane transporters to modulate intracranial pressure

Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge. Nevertheless, the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP. Here, we employed experimental rats to demonstrate low osmotic water permeability of the choroid plexus, lack of an osmotic gradient across this tissue, and robust CSF secretion against osmotic gradients. Together, these results illustrate that CSF secretion occurs independently of conventional osmosis, which challenges the existing assumption that CSF production is driven entirely by bulk osmotic forces across the CSF-secreting choroid plexus. Instead, we reveal that the choroidal Na+/K+/Cl- cotransporter NKCC1, Na+/HCO3- cotransporter NBCe2, and Na+/K+-ATPase are actively involved in CSF production and propose a molecular mode of water transport supporting CSF production in this secretory tissue. Further, we demonstrate that inhibition of NKCC1 directly reduces the ICP, illustrating that altered CSF secretion may be employed as a strategy to modulate ICP. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP.

neuroscience↗