Choroid Plexus Blood-CSF Barrier: Major Player in Brain Disease Modeling and Neuromedicine

Conrad Johanson
2018 Journal of Neurology and Neuromedicine  
The choroid plexus (CP) of the blood-cerebrospinal fluid barrier (BCSFB) impacts CSF homeostasis, brain diseases and neuromedical translation. CP executes neuroendocrine, excretory, and neuroimmune actions. BCSFB diversely manages brain-spinal cord fluid environments, giving rise to a wide pathophysiology spectrum. Newly-discovered choroidal phenomena include integration of circadian clock signals, immune interaction with gut microbiotica, and expression of receptors to taste CSF composition.
more » ... SFB tight junctions and transcellular mechanisms differ from blood-brain barrier (BBB) counterparts, variably regulating pathogen and leukocyte access to the CSF-brain nexus. This review highlights microbial agents, substrates and autoantigens using CP epithelial membranes to penetrate CSF and periventricular regions. Lipopolysaccharide (LPS) is analyzed as a barrier-damaging agent and neuroinflammation promoter. Transducing LPSand toll-like receptor activity produce CP-CSF cytokines in sickness behavior and virulent sepsis-associated encephalopathy. Agents/systems that counter oxidative activity such as matrix metalloproteinase 8 inhibitors and Nrf2 activators (bile acids and isothiocyanates) show promise as neural and CP protectants. One review theme emphasizes CP's preponderant role in initiating central diseases, and their remediation. In view of BCSFB permeativity alterations and epithelial transformation, we discuss: systemic lupus erythematosus, N-methyl D-aspartateassociated autoencephalitis, helicobacter disruption of BCSFB, toll-like receptor 2 stimulation in CP (neuroinflammation), the CP gateway for trypanosomes, and APOE-linked cholesterol transport into CSF. Another section treats concurrent involvement of BCSFB-BBB alterations in helminthic meningitis, forebrain ischemia, acute hyperthermia, leptin resistance/obesity, diabetes mellitus, and Alzheimertype neurodegeneration. Barrier impairment is analyzed by injury type, time course, therapeutic strategies, and translational neuromedicine principles. The restorative power of BCSFB-transported growth factors, hormones and medicinal agents is emphasized for strengthening CP-CSF homeostatic mechanisms in seizures, stroke and Parkinsonism. A worthy therapeutic aim is to attenuate CNS disorders triggered by BCSFB malfunction, using CSF-delivered therapeutic agents for promoting neural viability. Neuronal networks require stable extracellular fluid (ECF). Neurotransmission and electrical signaling depend on ECF of specialized composition. Transport/barrier/secretory systems at the blood-brain barrier (BBB) and blood-cerebrospinal fluid barrier (BCSFB) primarily regulate ECF. Choroid plexus (CP) is the main locus of the BCSFB, but circumventricular organs/meninges also contribute. There has been a tendency to underestimate BCSFB importance in favor of BBB. The two Johanson CE, Johanson NL. Choroid Plexus Blood-CSF Barrier: Major Player in Brain Disease Modeling and Neuromedicine.
doi:10.29245/2572.942x/2018/4.1194 fatcat:v64ilqhw4ndntanpuklkljdaxa