The Blood-CSF-Brain Route of Neurological Disease: The Indirect Pathway into the Brain.

Cousins, Oliver; Hodges, Angela; Schubert, Julia; Veronese, Mattia; Turkheimer, Federico; Miyan, Jaleel; Engelhardt, Britta; Roncaroli, Federico (2022). The Blood-CSF-Brain Route of Neurological Disease: The Indirect Pathway into the Brain. Neuropathology and applied neurobiology, 48(4), e12789. Wiley 10.1111/nan.12789

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The brain is protected by the endothelial blood-brain-barrier (BBB) that limits the access of micro-organisms, tumour cells, immune cells and autoantibodies to the parenchyma. However, the classic model of disease spread across a disrupted BBB does not explain the focal distribution of lesions seen in a variety of neurological diseases and why lesions are frequently adjacent to the cerebrospinal fluid (CSF) spaces. We have critically reviewed the possible role of a blood-CSF-brain route as a disease entry pathway into the brain parenchyma. The initial step of this pathway is the transfer of pathogens or immune components from the blood into the CSF at the choroid plexuses, where the blood-CSF-barrier (BCSFB) is located. The flow of CSF results in disease dissemination throughout the CSF spaces. Access to the brain parenchyma from the CSF, can then occur across the ependymal layer at the ventricular surface, or across the pial-glial barrier of the subarachnoid space and the Virchow-Robin spaces. We have reviewed the anatomy and physiology of the blood-CSF-brain pathway and the brain barriers controlling this process. We then summarised the evidence supporting this brain entry route in a cross-section of neurological diseases including neuromyelitis optica, multiple sclerosis, neurosarcoidosis, neuropsychiatric lupus, cryptococcal infection, and both solid and haematological tumours. This summary highlights the conditions that share the blood-CSF-brain pathway as a pathogenetic mechanism. These include the characteristic proximity of lesions to CSF, evidence of disruption of the brain barriers, and the identification of significant pathology within the CSF. An improved understanding of pathological transfer through the CSF and across all brain barriers will inform on more effective and targeted treatments of primary and secondary disease of the central nervous system.

Item Type:

Journal Article (Review Article)

Division/Institute:

04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute

UniBE Contributor:

Engelhardt, Britta

Subjects:

600 Technology > 610 Medicine & health

ISSN:

1365-2990

Publisher:

Wiley

Language:

English

Submitter:

Cindy Carolyn Alpinice Schumacher

Date Deposited:

27 Dec 2021 09:37

Last Modified:

23 Dec 2022 00:25

Publisher DOI:

10.1111/nan.12789

PubMed ID:

34935179

Uncontrolled Keywords:

Blood-brain-barrier Virchow-Robin spaces blood-CSF-barrier choroid plexus

BORIS DOI:

10.48350/163157

URI:

https://boris.unibe.ch/id/eprint/163157

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