Title:Merging Transport Data for Choroid Plexus with Blood-Brain Barrier to Model CNS Homeostasis and Disease More Effectively
Volume: 15
Issue: 9
Author(s): Conrad Johanson and Nancy Johanson
Affiliation:
Keywords:
Alzheimer’s disease, aquaporins, blood-CSF barrier, cerebrospinal fluid, choroidal epithelium, CSF
immunosurveilance, CSF sink, CSF translational research, ependyma, growth factors, hydrocephalus, hyperthermia, intracranial
pressure, neurochemistry, neuroendocrine, neurogenic regions, neurotrophins, stroke, traumatic brain injury, ventricles.
Abstract: 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.
