The Blood–Cerebrospinal Fluid Barrier: Structure and Functional Significance

Abstract

The choroid plexus (CP) of the blood-CSF barrier (BCSFB) displays fundamentally different properties than blood-brain barrier (BBB). With brisk blood flow (10 × brain) and highly permeable capillaries, the human CP provides the CNS with a high turnover rate of fluid (∼400,000 μL/day) containing micronutrients, peptides, and hormones for neuronal networks. Renal-like basement membranes in microvessel walls and underneath the epithelium filter large proteins such as ferritin and immunoglobulins. Type IV collagen (α3, α4, and α5) in the subepithelial basement membrane confers kidney-like permselectivity. As in the glomerulus, so also in CP, the basolateral membrane utrophin A and colocalized dystrophin impart structural stability, transmembrane signaling, and ion/water homeostasis. Extensive infoldings of the plasma-facing basal labyrinth together with lush microvilli at the CSF-facing membrane afford surface area, as great as that at BBB, for epithelial solute and water exchange. CSF formation occurs by basolateral carrier-mediated uptake of Na+, Cl-, and HCO3-, followed by apical release via ion channel conductance and osmotic flow of water through AQP1 channels. Transcellular epithelial active transport and secretion are energized and channeled via a highly dense organelle network of mitochondria, endoplasmic reticulum, and Golgi; bleb formation occurs at the CSF surface. Claudin-2 in tight junctions helps to modulate the lower electrical resistance and greater permeability in CP than at BBB. Still, ratio analyses of influx coefficients (Kin) for radiolabeled solutes indicate that paracellular diffusion of small nonelectrolytes (e.g., urea and mannitol) through tight junctions is restricted; molecular sieving is proportional to solute size. Protein/peptide movement across BCSFB is greatly limited, occurring by paracellular leaks through incomplete tight junctions and low-capacity transcellular pinocytosis/exocytosis. Steady-state concentration ratios, CSF/plasma, ranging from 0.003 for IgG to 0.80 for urea, provide insight on plasma solute penetrability, barrier permeability, and CSF sink action to clear substances from CNS.

Magnetic Resonance Imaging Reveals Therapeutic Effects of Interferon-Beta on Cytokine-Induced Reactivation of Rat Model of Multiple Sclerosis

“…However, gadolinium enhancement in the ipsilateral meninges, indicating breakdown of the blood-CSF barrier, was evident in the frrMOG-EAE animals. The B-CSF barrier (BCSFB) has a different composition and role to the BBB 42 and selective expression of cell adhesion molecules on the BCSFB has been reported during brain inflammation. 43 Although leukocytes can cross an intact BBB and BCSFB, breakdown of the BCSFB may facilitate presentation of chemokines and enhance recruitment to the meninges.…”

Blood–Brain Barrier Dysfunction as a Cause and Consequence of Alzheimer's Disease

“…These cells, like the BBB, have tight junctions that restrict paracellular diffusion of solutes and express specialized transporters that carefully regulate the molecular composition of CSF. 113 In humans, the entire CSF volume turns over B4 to 6 times per day. In AD, 114 this rate is markedly decreased because of a combination of decreased CSF production and increased CSF volume caused by brain atrophy and ventricular enlargement.…”

The Distributional Nexus of Choroid Plexus to Cerebrospinal Fluid, Ependyma and Brain

“…This reflects Na þ pump localization apically in CP (Parmelee and Johanson 1989) but basolaterally in PT. Still, the similar structural adaptations and transporter protein expression, CP versus PT, prompt comparisons of cross-reactions in the respective basement membrane-epithelial systems (Johanson, Stopa, and McMillan 2010). Many toxicologic effects on CP mimic damage to PT or other nephron regions (Levine 1987).…”