Affiliations: Neurochemisches Labor der Neurologischen Klinik,
Robert-Koch-Str. 40, Universität Göttingen, D – 37075 Göttingen,
Germany. Tel.: +49 551 39 66 19; Fax: +49 551 39 20 28; E-mail:
hreiber@med.uni-goettingen.de
Abstract: Cerebrospinal fluid (CSF) routine analysis for diagnosis of
neurological diseases is based on the concepts for discrimination of
blood-derived and brain-derived immunoglobulin fractions in CSF. The actual
molecular flux/CSF flow theory of the blood/CSF barrier function, which founded
the hyperbolic discrimination lines in quotient diagrams, is derived from the
laws of molecular diffusion combined with CSF flow rate. It emerged from this
theory that the decrease of CSF flow rate is sufficient to explain
quantitatively the increase of CSF protein concentrations as observed in many
neurological diseases. With this concept of CSF flow rate as the modulator of
the normal and pathological blood-CSF barrier function, we got for the first
time a theoretical frame work to explain also quantitatively the dynamics of
brain-derived proteins and their source related (neurons and glial cells or
leptomeningal cells) differences. The review of the anatomical, physiological
and biophysical knowledge points to the new interpretations: The changing
albumin quotient is an indicator of changing CSF flow rate and not for a
morphological "leakage" of the blood-brain barrier. As an application of these concepts the dynamics of brain-derived
molecules in blood are discussed with two examples: beta trace protein, flowing
with CSF into venous blood, and neuron-specific enolase, passing from tissue
into blood the opposite direction of serum proteins, again a gradient-dependent
protein diffusion across the intact blood vessel wall.
Keywords: blood-CSF barrier function, blood-brain barrier, Cerebrospinal fluid, CSF flow, brain-derived proteins, blood-derived proteins, protein dynamics, theory
