Intracranial pressure elevation alters CSF clearance pathways
Open Access
- 16 April 2020
- journal article
- research article
- Published by Springer Science and Business Media LLC in Fluids and Barriers of the CNS
- Vol. 17 (1), 1-19
- https://doi.org/10.1186/s12987-020-00189-1
Abstract
Infusion testing is a common procedure to determine whether shunting will be beneficial in patients with normal pressure hydrocephalus. The method has a well-developed theoretical foundation and corresponding mathematical models that describe the CSF circulation from the choroid plexus to the arachnoid granulations. Here, we investigate to what extent the proposed glymphatic or paravascular pathway (or similar pathways) modifies the results of the traditional mathematical models. We used a compartment model to estimate pressure in the subarachnoid space and the paravascular spaces. For the arachnoid granulations, the cribriform plate and the glymphatic circulation, resistances were calculated and used to estimate pressure and flow before and during an infusion test. Finally, different variations to the model were tested to evaluate the sensitivity of selected parameters. At baseline intracranial pressure (ICP), we found a very small paravascular flow directed into the subarachnoid space, while 60% of the fluid left through the arachnoid granulations and 40% left through the cribriform plate. However, during the infusion, 80% of the fluid left through the arachnoid granulations, 20% through the cribriform plate and flow in the PVS was stagnant. Resistance through the glymphatic system was computed to be 2.73 mmHg/(mL/min), considerably lower than other fluid pathways, giving non-realistic ICP during infusion if combined with a lymphatic drainage route. The relative distribution of CSF flow to different clearance pathways depends on ICP, with the arachnoid granulations as the main contributor to outflow. As such, ICP increase is an important factor that should be addressed when determining the pathways of injected substances in the subarachnoid space. Our results suggest that the glymphatic resistance is too high to allow for pressure driven flow by arterial pulsations and at the same time too small to allow for a direct drainage route from PVS to cervical lymphatics.Keywords
Funding Information
- H2020 European Research Council (714892)
- Norges Forskningsråd (250731)
- Swedish National Space Agency (193/17)
This publication has 89 references indexed in Scilit:
- Evaluating glymphatic pathway function utilizing clinically relevant intrathecal infusion of CSF tracerJournal of Translational Medicine, 2013
- Parameter estimations for the cerebrospinal fluid infusion testMathematical Medicine and Biology, 2012
- Three-dimensional computational prediction of cerebrospinal fluid flow in the human brainComputers in Biology and Medicine, 2011
- Recent insights into a new hydrodynamics of the cerebrospinal fluidBrain Research Reviews, 2011
- The function and structure of the cerebrospinal fluid outflow systemFluids and Barriers of the CNS, 2010
- Cerebrospinal fluid dynamics in the human cranial subarachnoid space: an overlooked mediator of cerebral disease. II. In vitro arachnoid outflow modelJournal of The Royal Society Interface, 2010
- Structure and function of the blood–brain barrierNeurobiology of Disease, 2010
- A vascular anatomical network model of the spatio-temporal response to brain activationNeuroImage, 2008
- Human arachnoid granulations Part I: a technique for quantifying area and distribution on the superior surface of the cerebral cortexFluids and Barriers of the CNS, 2007
- CSF outflow resistance as predictor of shunt function. A long-term studyActa Neurologica Scandinavica, 2004