Evaluation of the blood-CSF barrier by protein gradients and the humoral immune response within the central nervous system.

A linear correlation was found between the serum/cerebrospinal fluid (CSF) concentration ratios of albumin, caeruloplasmin and alpha2-macroglobulin and their hydrodynamic radii in a semilogarithmic plot. This protein gradient is used as a parameter to evaluate the blood-CSF barrier under normal and pathological conditions. Irrespective of vastly different transfer rates, the ratio/size permeation curves of proteins at the blood-CSF barrier and the blood-lymph barrier have comparable characteristics. Therefore the protein gradients found in various disease states are interpreted by means of Renkin's general law of lymph formation. Declined gradients are caused either by an increased permeability of the barrier sites or by a decreased turnover rate of the CSF within the compartment punctured. The concentration ratios of immunoglobulins are related to the gradient that is constructed with the ratios of the barrier-indicative marker proteins. As judged by comparative disc electrophoresis of serum and CSF, those disease states that are dominated by barrier impairment are used to establish the range of concentration ratios, compatible with a passive immunoglobulin transfer in any condition in which the barrier is disordered. A mathematical approach is described, which allows the quantitative evaluation of the minimal immunoglobulin portion that is synthesized within the central nervous system.