Abstract
Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction. Frequently used interpretations such as barrier leakage, disruption or breakdown contradict CSF protein data, which suggest a reduced CSF flow rate as the cause. Even the severest barrier dysfunctions do not change the molecular size-dependent selectivity or the interindividual variation of the protein transfer across barriers. Serum protein concentrations in lumbar CSF increase with hyperbolic functions, but the levels of proteins that do not pass the barrier remain constant (brain proteins) or increase linearly (leptomeningal proteins). All CSF protein dynamics above and below a lumbar blockade can also be explained, independent of their barrier passage, by a reduced caudally directed flow. Local accumulation of gadolinium in multiple sclerosis (MS) is now understood as due to reduced bulk flow elimination by interstitial fluid (ISF). Nonlinear change of the steady state in barrier dysfunction and along normal rostro-caudal gradients supports the diffusion/flow model and contradicts obstructions of diffusion pathways. Regardless of the cause of the disease, pathophysiological flow blockages are found in bacterial meningitis, leukemia, meningeal carcinomatosis, Guillain-Barré syndrome, MS and experimental allergic encephalomyelitis. In humans, the fortyfold higher albumin concentrations in early fetal development decrease later with maturation of the arachnoid villi, i.e., with beginning CSF outflow, which contradicts a relevant outflow to the lymphatic system. Respiration- and heartbeat-dependent oscillations do not disturb net direction of CSF flow. Blood-CSF and blood-brain barrier dysfunctions are an expression of reduced CSF or ISF flow rate.
Highlights
Increased concentrations of serum proteins in cerebrospinal fluid (CSF) are interpreted as blood-CSF barrier dysfunction
In normal CSF, the concentrations of blood-derived proteins increase along the CSF flow way through the subarachnoid space (SAS)[41,42,43] because of the steady diffusion of proteins from capillaries accompanying the SAS
What happens if there is a pathological increase in serum protein concentrations in the CSF? What about those cases where so many authors speak of “barrier leakage”?
Summary
Many neurological diseases[1,2] are associated with an increased concentration of blood-derived proteins in cerebrospinal fluid (CSF), interpreted as a dysfunction of the blood-CSF or blood-brain barrier[3,4,5]. Generations of neurophysiologists and neuropathologists[3,4,5,16,17,18,19,20] have contributed sophisticated knowledge about the specific structures and functions of the biological barriers in the brain, with the intercellular tight junctions in the capillary endothelium, meningeal epithelium, choroidal plexus ependyma and arachnoid epithelium being most prominent[4,18,19,20] This illustrative work on the morphology of the normal barriers has completely obscured the view of CSF flow as the main modulating parameter for the barrier function for proteins in pathological processes[3,7,8,15]. It is the aim of this review to show the data that will help to resolve this hindrance in the development of new diagnostic approaches and therapies in neurology
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have