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

Abstract

Bordering the ventricular cerebrospinal fluid (CSF) are epithelial cells of choroid plexus (CP), ependyma and circumventricular organs (CVOs) that contain homeostatic transporters for mediating secretion/reabsorption. The distributional pathway (''nexus'') of CP-CSF-ependyma-brain furnishes peptides, hormones, and micronutrients to periventricular regions. In disease/toxicity, this nexus becomes a conduit for infectious and xenobiotic agents. The sleeping sickness trypanosome (a protozoan) disrupts CP and downstream CSF-brain. Piperamide is anti-trypanosomic but distorts CP epithelial ultrastructure by engendering hydropic vacuoles; this reflects phospholipidosis and altered lysosomal metabolism. CP swelling by vacuolation may occlude CSF flow. Toxic drug tools delineate injuries to choroidal compartments: cyclophosphamide (vasculature), methylcellulose (interstitium), and piperazine (epithelium). Structurally perturbed CP allows solutes to penetrate the ventricles. There, CSF-borne pathogens and xenobiotics may permeate the ependyma to harm neurogenic stem cell niches. Amoscanate, an anti-helmintic, potently injures rodent ependyma. Ependymal/brain regions near CP are vulnerable to CSF-borne toxicants; this proximity factor links regional barrier breakdown to nearby periventricular pathology. Diverse diseases (e.g., African sleeping sickness, multiple sclerosis) take early root in choroidal, circumventricular, or perivascular loci. Toxicokinetics informs on pathogen, anti-parasitic agent, and auto-antibody distribution along the CSF nexus. CVOs are susceptible to plasma-borne toxicants/pathogens. Countering the physico-chemical and pathogenic insults to the homeostasis-mediating ventricle-bordering cells sustains brain health and fluid balance.

Regulation of cerebrospinal fluid (CSF) flow in neurodegenerative, neurovascular and neuroinflammatory disease

“…The CP may be directly damaged by either ischemic or traumatic injury, leading to the breakdown of the BCSFB and the accumulation of fluid within the cranium. Compounding these effects, debris mobilized within the CSF from the ischemic or traumatic lesion may interrupt CSF flow and block CSF reabsorption sites, leading to a dangerous increase in intracranial pressure that can result in further tissue ischemia and ultimately brain herniation [102, 103]. Breakdown of the BCSFB following ischemic or traumatic brain injury may also increase its permeability to leukocyte trafficking, promoting immune cell infiltration into the injured brain [104].…”

Planar Organization of Multiciliated Ependymal (E1) Cells in the Brain Ventricular Epithelium

“…How translational polarity in E1 cells contributes to CSF flow and/or functions of brain remains unknown. The open apical surface generated by the displacement of motile cilia in E1 cells might provide cell-surface for the secretion of chemokines such as Noggin that promotes adult neurogenesis in the ventricular-subventricular zone (V-SVZ, see GLOSSARY) [40], absorption and transport of factors from/to the CSF [41], and/or synapse-like contacts with supraepedymal axons from serotonergic neurons in the raphe [42–46]. Administration of serotonin in rat brainstem slices increases ciliary beating frequency on E1 cells [47].…”

Plasminogen in cerebrospinal fluid originates from circulating blood

“…These in vivo data suggest that circulating plasminogen enters the CSF at the choroid plexus. This enormous epithelial/endothelial surface area is potentially available for untoward leakage of plasma proteins into CSF [33,34]. Because LPS is also known to induce interference with the integrity of the glomerular filtration barrier [35], we also investigated the passage of plasminogen through the renal glomerulus.…”