Spera, Irene; Cousin, Nikola; Ries, Miriam; Kedracka, Anna; Castillo, Alina; Aleandri, Simone; Vladymyrov, Mykhailo; Mapunda, Josephine A; Engelhardt, Britta; Luciani, Paola; Detmar, Michael; Proulx, Steven T (2023). Open pathways for cerebrospinal fluid outflow at the cribriform plate along the olfactory nerves. EBioMedicine, 91(104558), p. 104558. Elsevier 10.1016/j.ebiom.2023.104558
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BACKGROUND
Routes along the olfactory nerves crossing the cribriform plate that extend to lymphatic vessels within the nasal cavity have been identified as a critical cerebrospinal fluid (CSF) outflow pathway. However, it is still unclear how the efflux pathways along the nerves connect to lymphatic vessels or if any functional barriers are present at this site. The aim of this study was to anatomically define the connections between the subarachnoid space and the lymphatic system at the cribriform plate in mice.
METHODS
PEGylated fluorescent microbeads were infused into the CSF space in Prox1-GFP reporter mice and decalcification histology was utilized to investigate the anatomical connections between the subarachnoid space and the lymphatic vessels in the nasal submucosa. A fluorescently-labelled antibody marking vascular endothelium was injected into the cisterna magna to demonstrate the functionality of the lymphatic vessels in the olfactory region. Finally, we performed immunostaining to study the distribution of the arachnoid barrier at the cribriform plate region.
FINDINGS
We identified that there are open and direct connections from the subarachnoid space to lymphatic vessels enwrapping the olfactory nerves as they cross the cribriform plate towards the nasal submucosa. Furthermore, lymphatic vessels adjacent to the olfactory bulbs form a continuous network that is functionally connected to lymphatics in the nasal submucosa. Immunostainings revealed a discontinuous distribution of the arachnoid barrier at the olfactory region of the mouse.
INTERPRETATION
Our data supports a direct bulk flow mechanism through the cribriform plate allowing CSF drainage into nasal submucosal lymphatics in mice.
FUNDING
This study was supported by the Swiss National Science Foundation (310030_189226), Dementia Research Switzerland-Synapsis Foundation, the Heidi Seiler Stiftung and the Fondation Dr. Corinne Schuler.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
09 Interdisciplinary Units > Microscopy Imaging Center (MIC) 04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute 08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Spera, Irene, Aleandri, Simone, Vladymyrov, Mykhailo, Mapunda, Josephine Angelo, Engelhardt, Britta, Luciani, Paola, Proulx, Steven Thomas |
Subjects: |
600 Technology > 610 Medicine & health 500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
2352-3964 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
13 Apr 2023 12:12 |
Last Modified: |
20 Sep 2024 08:38 |
Publisher DOI: |
10.1016/j.ebiom.2023.104558 |
PubMed ID: |
37043871 |
Uncontrolled Keywords: |
Arachnoid barrier Cerebrospinal fluid Cribriform plate Lymphatic vessels Olfactory nerves |
BORIS DOI: |
10.48350/181695 |
URI: |
https://boris.unibe.ch/id/eprint/181695 |
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