Dynamics of brain-derived proteins in cerebrospinal fluid

• Published in: Clinica chimica acta Vol. 310; no. 2; pp. 173 - 186
• Main Author: Reiber, Hansotto
• Format: Journal Article
• Language: English
• Published: Shannon Elsevier B.V 20.08.2001; Elsevier
• Subjects: Albumins - cerebrospinal fluid; Biological and medical sciences; Biophysical Phenomena; Biophysics; Blood Proteins - cerebrospinal fluid; Blood-Brain Barrier - physiology; Blood–CSF barrier function; Brain Chemistry; Carcinoembryonic antigen (CEA); Cerebrospinal fluid (biochemistry, cytology, circulation, manometry). Intracranial pressure determination; Cerebrospinal fluid (CSF); CSF flow; Cystatin C; Cystatins - cerebrospinal fluid; Humans; Intramolecular Oxidoreductases - cerebrospinal fluid; Investigative techniques, diagnostic techniques (general aspects); Lipocalins; Medical sciences; Meninges - chemistry; Models, Biological; Nerve Tissue Proteins - cerebrospinal fluid; Neuron-specific enolase (NSE); Phosphopyruvate Hydratase - blood; Prealbumin - cerebrospinal fluid; S-100 protein; S100 Proteins - blood; Soluble intercellular adhesion molecule (s-ICAM); Tau protein; tau Proteins - cerebrospinal fluid; Transthyretin; β-trace protein (prostaglandin D synthase); Blood–CSF barrier function; Soluble intercellular adhesion molecule (s-ICAM); CSF flow; Neuron-specific enolase (NSE); Cerebrospinal fluid (CSF); Tau protein; Carcinoembryonic antigen (CEA); S-100 protein; Cystatin C; Transthyretin; β-trace protein (prostaglandin D synthase); Human; Nervous system diseases; Biochemical analysis; Central nervous system disease; Parkinson disease; Exploration; Degenerative disease; Cerebrospinal fluid; Protein; Cerebral disorder; Extrapyramidal syndrome
• ISSN: 0009-8981; 1873-3492
• DOI: 10.1016/S0009-8981(01)00573-3

Background: The recent theory of blood–cerebrospinal fluid (CSF) barrier function and dysfunction connects molecular flux and CSF flow rate. A reduced CSF flow rate is sufficient to account for the observed hyperbolic relation between different blood-derived protein concentrations in CSF in cases of a blood–CSF barrier dysfunction. Methods: The dynamics of brain-derived proteins in CSF are investigated with reference to the CSF flow rate measured by CSF/serum albumin concentration quotient. Results: Proteins from neurons or glial cells, tau protein, neuron-specific enolase, S-100 protein, all enter CSF primarily in the ventricular and cisternal space. Their concentration between normal ventricular and lumbar CSF is decreasing (in contrast to blood-derived proteins), and in the case of pathologically decreasing CSF flow rate, the concentration in lumbar CSF remains invariantly constant. Concentrations of the primarily leptomeningeal proteins, β-trace protein and cystatin C, increase between normal ventricular and lumbar CSF, and in the case of pathologically decreased CSF flow rate they increase linearly in lumbar CSF (concentrations of blood-derived proteins increase non-linearly). Conclusions: A satisfactory physiological explanation can now be given for the dynamics of proteins in CSF consisting of both brain- and blood-derived fractions (transthyretin, soluble intercellular adhesion molecule (s-ICAM)), as well as the disputed decrease of leptomeningeal protein concentrations (β-trace protein, cystatin C) in cases of bacterial meningitis is also explained. The biophysical treatment of dynamics in the ventricular and lumbar CSF extends the new theory and shows that CSF flow rate is the most relevant parameter for understanding the pathological changes of both blood- and brain-derived proteins in CSF. The impact on diagnosis of neuro-degenerative diseases is discussed.