Molecular anatomy and functions of the choroidal blood-cerebrospinal fluid barrier in health and disease

Abstract

The barrier between the blood and the ventricular cerebrospinal fluid (CSF) is located at the choroid plexuses. At the interface between two circulating fluids, these richly vascularized veil-like structures display a peculiar morphology explained by their developmental origin, and fulfill several functions essential for CNS homeostasis. They form a neuroprotective barrier preventing the accumulation of noxious compounds into the CSF and brain, and secrete CSF, which participates in the maintenance of a stable CNS internal environment. The CSF circulation plays an important role in volume transmission within the developing and adult brain, and CSF compartments are key to the immune surveillance of the CNS. In these contexts, the choroid plexuses are an important source of biologically active molecules involved in brain development, stem cell proliferation and differentiation, and brain repair. By sensing both physiological changes in brain homeostasis and peripheral or central insults such as inflammation, they also act as sentinels for the CNS. Finally, their role in the control of immune cell traffic between the blood and the CSF confers on the choroid plexuses a function in neuroimmune regulation and implicates them in neuroinflammation. The choroid plexuses, therefore, deserve more attention while investigating the pathophysiology of CNS diseases and related comorbidities.

Complement activation contributes to perioperative neurocognitive disorders in mice

“…The choroid plexus also constitutively expresses markers of epithelial cells such as ICAM-1 and VCAM-1 [45]. Upon activation, they mediate leukocyte infiltration into the CNS [46]. Here, we found that ICAM-1 and VCAM-1 were markedly increased in the choroid plexus postoperatively, suggesting surgery activates choroidal epithelium.…”

A cellular and spatial map of the choroid plexus across brain ventricles and ages

“…Several topics (3,6,11,14,16,23) were differentially weighted across cells from the different brain regions (Fig. S3C), including genes encoding transporters (Fig.…”

“…Built as an epithelial bilayer with an accompanying network of predominantly non-neural cell types and vasculature, the ChP regulates the secretion and composition of CSF that fills the brain's ventricles, bathes stem cells, and reaches neurons via exchange with the interstitial fluid 1 . CSF composition is regulated by de novo synthesis and secretion of signals by epithelial cells, as well as selective transcytosis of blood-borne factors [2][3][4][5] , which regulate neurogenesis 6,7 or guide migration of newborn neurons 8 .…”

“…The ChP is also sensitive to peripheral body signals, and arousal states 9,10 and gates immune cell passage from body to brain 3,[11][12][13] . Disrupted ChP function and CSF composition, as well as abnormal CSF volume and ventricle space, are common to neurologic disease, including brain inflammation 14 , autism 15,16 , schizophrenia 17 , and Alzheimer's disease 18,19 .…”

The choroid plexus: Simple structure, complex functions

“…Due to the close proximity to the subventricular zone and to the influence of the CSF in the subgranular zone of the dentate gyrus of the hippocampus (Lun, Monuki, & Lehtinen, 2015;Marques et al, 2017), the CP-CSF system and CP-born molecules have a significant role in adult brain neurogenesis. Moreover, the CP synthesizes and secretes biologically active molecules crucial for brain development, stem cell differentiation, and brain repair (Ghersi-Egea et al, 2018;Planques, Oliveira Moreira, Dubreuil, Prochiantz, & Nardo, 2019). Hence, the CP plays a pivotal role in maintaining brain local microenvironment and CNS homeostasis.…”