Study of protein characteristics that influence entry into the cerebrospinal fluid of normal mice and mice with encephalitis.

Abstract

A B S T R A C T Entry of proteins into the cerebrospinal fluid (CSF) from the blood is partially determined by the size of the protein. To determine whether other characteristics of proteins influence CSF entry, proteins or protein fragments were iodinated, inoculated intravenously, and serum and CSF were sampled at later times. The Fc fragment of immunoglobulin G (IgG) did not enter the CSF significantly better than the Fab fragment suggesting that choroidal Fc receptors are not of importance for selective immunoglobulin entry. To determine the role of protein charge on entry, bovine serum albumin [isoelectric point (pI) = 3.9] was chemically altered to provide an albumin with an average pI of 6 (A-6) and another with a pl of 8.5 (A-8). All albumins were of the same size on sodium dodecyl sulfate-polyacrylamide gel electrophoresis. A-8 entered the CSF -10-fold better than the native albumin. A-6 was intermediate, entering approximately twofold better. At the time of increased CSF protein concentration during an acute viral encephalitis these differences were narrowed but not eliminated. It is concluded that charge is an important determinant of protein entry into the CSF.

Recovery from viral encephalomyelitis: immune-mediated noncytolytic virus clearance from neurons

“…Antibody is likely to participate in control, as well as initial clearance, and there are two mechanisms for maintaining antibody in the CNS: passage of immunoglobulin from the blood across the BBB into the brain parenchyma or local production of antibody by antibody-secreting cells that are resident in the CNS. Although the BBB normally restricts the entry of proteins from the blood into the CNS, this function is compromised by the inflammatory response during the acute phase of infection and plasma antibody enters the CNS in larger amounts than during recovery when the barrier has healed [60][61][62]. With a normally functioning BBB, interstitial brain levels of antibody are 1:100-1:200 of plasma levels, a level that may be inadequate for long-term control.…”

Blood-brain barrier transport of cationized immunoglobulin G: enhanced delivery compared to native protein.

“…Cationization of proteins is known to, in general, enhance their cellular uptake (5)(6)(7). Cationization of albumin increases the transport of this plasma protein across the blood-cerebrospinal fluid (CSF) barrier-i.e., the choroid plexus-into CSF (8) and across the brain capillary wall into brain interstitial fluid (9). BBB transport of cationized albumin demonstrates time and temperature dependence and is saturable, and this process, called absorptive-mediated transcytosis (10), has characteristics similar to receptor-mediated transport mechanisms (11).…”

Enhanced permeabilities of cationized‐bovine serum albumins at the blood‐nerve and blood‐brain barriers in awake rats

“…fluid (Griffin and Giffels, 1982), and other organs (Shen and Ryser, 1978;Adler et al, 1983;Bergmann et al, 1985).…”

“…In brief, dialyzed nBSA (Fluka, Ronkonkoma, NY) was activated by carbodiimide (Fluka) and then treated with ethylene diamine (Fluka) at pH = 4.75, T = 23°C (Griffin and Giffels, 1982;Shimon-Hophy et al, 1991). The solution then was dialyzed against distilled water for 3 days, followed by lyophilization.…”