Choroid plexus and the blood–cerebrospinal fluid barrier in disease

Abstract

The choroid plexus (CP) forming the blood-cerebrospinal fluid (B-CSF) barrier is among the least studied structures of the central nervous system (CNS) despite its clinical importance. The CP is an epithelio-endothelial convolute comprising a highly vascularized stroma with fenestrated capillaries and a continuous lining of epithelial cells joined by apical tight junctions (TJs) that are crucial in forming the B-CSF barrier. Integrity of the CP is critical for maintaining brain homeostasis and B-CSF barrier permeability. Recent experimental and clinical research has uncovered the significance of the CP in the pathophysiology of various diseases affecting the CNS. The CP is involved in penetration of various pathogens into the CNS, as well as the development of neurodegenerative (e.g., Alzheimer´s disease) and autoimmune diseases (e.g., multiple sclerosis). Moreover, the CP was shown to be important for restoring brain homeostasis following stroke and trauma. In addition, new diagnostic methods and treatment of CP papilloma and carcinoma have recently been developed. This review describes and summarizes the current state of knowledge with regard to the roles of the CP and B-CSF barrier in the pathophysiology of various types of CNS diseases and sets up the foundation for further avenues of research. Publisher's NoteSpringer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Neutrophils: Underestimated Players in the Pathogenesis of Multiple Sclerosis (MS)

“…Genetically susceptible individuals display defects in peripheral immune regulation which lowers the barrier for activation of autoreactive T cells, which occurs in the lymphoid organs [ 29 , 38 ]. Following their activation, peripheral T cells are able to pass the blood–brain barrier (BBB)/blood–spinal cord barrier (BSCB), choroid plexus or meninges and may enter the CNS under specific conditions where they become reactivated after encountering CNS-related autoantigens, presented by MHC II molecules on APCs [ 29 , 39 , 40 , 41 ]. The recent discovery of meningeal lymphatic vessels that link to both CNS immunosurveillance and neuroinflammation suggests that autoimmune T cells may also drain to the cervical LNs, contributing to epitope spreading to the periphery [ 42 ].…”

The potential role of microvascular pathology in the neurological manifestations of coronavirus infection

“…TNF-alpha) that may be neurotoxic [ 33 ]. CNS Invasion via the blood-cerebrospinal fluid (B-CSF) barrier Many viruses invade the CNS via infection of epithelial cells of the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus, located in the ventricles of the brain [ 50 , 51 ]. The choroid plexus is an epithelia-endothelial convolute with highly vascularized stroma, fenestrated capillaries, and epithelial cells joined by tight junctions [ 51 ].…”

“… CNS Invasion via the blood-cerebrospinal fluid (B-CSF) barrier Many viruses invade the CNS via infection of epithelial cells of the blood-cerebrospinal fluid (B-CSF) barrier in the choroid plexus, located in the ventricles of the brain [ 50 , 51 ]. The choroid plexus is an epithelia-endothelial convolute with highly vascularized stroma, fenestrated capillaries, and epithelial cells joined by tight junctions [ 51 ]. Systemic inflammation following exposure to bacterial endotoxins, blood products following hemorrhage, and injury following ischemic stroke, alters gene expression in the choroid plexus.…”

“…These processes were also shown to upregulate other factors that affect B-CSF barrier permeability and immune cell trafficking (e.g. MMP-8, TNF-alpha, IL-6, IL-1B, MCP-1, and ICAM-1) [ 51 , 54 – 56 ]. The role of the choroid plexus and circumventricular organs in SARS-CoV-2 neuropathology remains unknown.…”

“…Potential routes of coronavirus CNS neuroinvasionand immune cell trafficking (e.g. MMP-8, TNF-alpha, IL-6, IL-1B, MCP-1, and ICAM-1)[51,[54][55][56]. The role of the choroid plexus and circumventricular organs in SARS-CoV-2 neuropathology remains unknown.…”