![]() CSF dynamics are finely tuned to ensure stable brain water content and an intracranial pressure (ICP) within the physiological range. The CSF disperses in the brain prior to entering the proposed exit routes along the lymphatic and/or perineural pathways. The CSF is replenished at a rate of approximately 500 ml/day in the adult human, the majority of which is secreted across the choroid plexus epithelium residing in the ventricles. The CSF protects the brain from mechanical insults and serves as a route for dispersion of hormones, nutrients, and metabolites between brain structures and neighboring cells. Our brain contains 80% water as the major constituent of the cerebrospinal fluid (CSF) that surrounds the brain tissue and fills the ventricles, the interstitial and intracellular fluid, and the blood contained in the cerebral vasculature. These insights identify new promising therapeutic targets against brain pathologies associated with elevated ICP. Therapeutic modulation of the rate of CSF secretion may be employed as a strategy to modulate ICP. ConclusionsĬSF secretion appears to not rely on conventional osmosis, but rather occur by a concerted effort of different choroidal transporters, possibly via a molecular mode of water transport inherent in the proteins themselves. ![]() We demonstrate that pharmacological modulation of CSF secretion directly affects the ICP. Instead, the CSF secretion across the luminal membrane of choroid plexus relies approximately equally on the Na +/K +/2Cl − cotransporter NKCC1, the Na +/HCO 3 − cotransporter NBCe2, and the Na +/K +-ATPase, but not on the Na +/H + exchanger NHE1. We demonstrate that CSF secretion can occur independently of conventional osmosis and that local osmotic gradients do not suffice to support CSF secretion. CSF and blood extractions from rats, pigs, and humans were employed for osmolality determinations and a mathematical model employed to determine a contribution from potential local gradients at the surface of choroid plexus. MethodsĮxperimental rats were employed for in vivo determinations of CSF secretion rates, ICP, blood pressure and ex vivo excised choroid plexus for morphological analysis and quantification of expression and activity of various transport proteins. Nevertheless, the details underlying the molecular mechanisms governing cerebrospinal fluid (CSF) secretion are largely unresolved, thus preventing targeted and efficient pharmaceutical therapy of cerebral pathologies involving elevated ICP. Disturbances in the brain fluid balance can lead to life-threatening elevation in the intracranial pressure (ICP), which represents a vast clinical challenge.
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