Non-linear ventriculo – Lumbar protein gradients validate the diffusion-flow model for the blood-CSF barrier

Abstract

BackgroundConcentrations of blood-derived proteins increase non-linearly between ventricular and lumbar CSF, which could not be satisfactorily explained by known barrier models. MethodsProtein data analysis with OriginLab. Interpretations with Quotient diagrams by CSF/ Statistics software. Results1. Nonlinearly increasing protein concentrations between ventricular and lumbar CSF are fitting to a Gaussian error function, the differential of the nonlinear concentration distribution function between blood and CSF. Increasing CSF protein concentrations (changing steady state), either due to barrier dysfunctions with reduced CSF flow rate or due to normal steady influx along the rostro-caudal flow path, increase the local gradient at the diffusion flow interface and thus the molecular current through the barrier.2. With a time- and space-related derivation, the hyperbolic relation between two molecules in CSF (e.g., QIgG: QAlb in quotient diagrams) is independent of the position in subarachnoid space: The reference line, Qlim, in quotient diagrams allows detection of intrathecal synthesis in ventricular, cisternal and lumbar CSF. Detection of intrathecal synthesis is not influenced by CSF extraction volume, only the barrier function, QAlb, is volume sensitive. ConclusionsCommon biophysics for barrier dysfunction and normal protein gradients provide additional evidence for the diffusion-flow interface model for barrier functions.