Blood-cerebrospinal fluid (CSF) barrier dysfunction means reduced CSF flow not barrier leakage - conclusions from CSF protein data

ABSTRACT Background: Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced flow rate the cause. Results: Even severest dysfunctions do not change molecular size-dependent selectivity interindividual variation transfer across barriers. Serum lumbar increase with hyperbolic functions, but levels that pass remain constant (brain proteins) linearly (leptomeningal proteins). All dynamics above and below blockade can also be explained, independent their passage, by caudally directed flow. Local accumulation gadolinium multiple sclerosis (MS) is now understood due to bulk elimination interstitial (ISF). Nonlinear steady state dysfunction along normal rostro-caudal gradients supports diffusion/flow model contradicts obstructions diffusion pathways. Regardless cause disease, pathophysiological blockages found bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS experimental allergic encephalomyelitis. In humans, fortyfold higher albumin early fetal development decrease later maturation arachnoid villi, i.e., beginning outflow, relevant outflow lymphatic system. Respiration- heartbeat-dependent oscillations disturb net direction Conclusion: Blood-CSF blood-brain an expression ISF rate.