Microvascular Blood-brain Barrier Research Articles

Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively.

Robust modeling of CNS transport integrates molecular fluxes at the microvascular blood-brain barrier and epithelial choroid plexus blood-cerebrospinal fluid (CSF) barrier. Normal activity of solute transporters, channels and aquaporins, in the cerebral endothelium and choroidal epithelium, sets the microenvironment composition for neurons and glia. Conversely, perturbed transport/permeability at the barrier interfaces causes interstitial fluid dyshomeostasis (e.g. edema) arising in neural disorders. Critically-important transependymal solute/water distribution between brain and CSF needs more attention. This treatise encourages procuring transport data simultaneously for blood-brain barrier, blood-CSF barrier and CSF. In situ perfusion and multicompartmental analyses (tracers, microdialysis) provide dynamic assessments of molecular transfer among various CNS regions. Diffusion, active transport and convection are distorted by disease- and age-associated alterations in barrier permeability and CSF turnover (sink action). Clinical complications result from suboptimal conveyance of micronutrients (folate), catabolites (β-amyloid) and therapeutic agents (antibiotics) within the CNS. Neurorestorative therapies for stroke, traumatic brain injury, multiple sclerosis and brain tumors are facilitated by insight on molecular and cellular trafficking through the choroid plexus-CSF nexus. Knowledge is needed about fluxes of growth factors, neurotrophins, hormones and leukocytes from ventricular CSF into the hippocampus, subventricular zone and hypothalamus. CSF and brain removal of potentially toxic catabolites and neuropeptides merits further investigation to manage the degeneration of Alzheimer's disease and normal pressure hydrocephalus. Novel therapies will rely on delineating peptide and drug distributions across the blood-brain barrier and choroid plexus-CSF, and how they modulate the intervening neural-glial networks and neurogenic sites. Multicompartmental transport modeling is key to devising specific pharmacologic targeting and thus impactful CSF translational research for CNS disorders.

Lipid synthesis by rat brain microvessel endothelial cells in tissue culture.

Lipid synthesis and its regulation by serum lipoproteins at the microvascular blood-brain barrier were studied using primary cultures of microvascular endothelial cells from rat brain. These cells are capable of synthesizing all their lipids (neutral lipids, phospholipids, glycolipids) from the water-soluble compounds, glucose, acetate, acetoacetate and beta-hydroxybutyrate. The ketone bodies, especially acetoacetate, are the preferred substrates for lipid synthesis. The incorporation patterns of acetate, acetoacetate and beta-hydroxybutyrate are very similar, indicating that these precursors contribute to lipid synthesis via the same metabolic route. However, the metabolic pathway is different for glucose, which is preferentially incorporated into phospholipids. The existence of an inverse relationship between lipid synthesis and the serum lipoprotein concentration suggests that cultured cerebral endothelial cells are capable of taking up lipids, principally cholesterol, contained in the serum lipoproteins. Cellular lipids would thus be supplied both by intracellular lipid synthesis and by serum lipoproteins. The difference between cholesterol synthesis rates in cultured cerebral endothelial cells and in isolated brain microvessel cells could be partly explained by the fact that the lipoprotein concentration is much lower in the culture medium than in rat serum.