Madarasz, Adrian; Xin, Li; Proulx, Steven T (2024). Clearance of erythrocytes from the subarachnoid space through cribriform plate lymphatics in female mice. EBioMedicine, 107(105295), p. 105295. Elsevier 10.1016/j.ebiom.2024.105295
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BACKGROUND
Atraumatic subarachnoid haemorrhage (SAH) is associated with high morbidity and mortality. Proposed mechanisms for red blood cell (RBC) clearance from the subarachnoid space (SAS) are erythrolysis, erythrophagocytosis or through efflux along cerebrospinal fluid (CSF) drainage routes. We aimed to elucidate the mechanisms of RBC clearance from the SAS to identify targetable efflux pathways.
METHODS
Autologous fluorescently-labelled RBCs along with PEGylated 40 kDa near-infrared tracer (P40D800) were infused via the cisterna magna (i.c.m.) in female reporter mice for lymphatics or for resident phagocytes. Drainage pathways for RBCs to extracranial lymphatics were evaluated by in vivo and in situ near-infrared imaging and by immunofluorescent staining on decalcified cranial tissue or dural whole-mounts.
FINDINGS
RBCs drained to the deep cervical lymph nodes 15 min post i.c.m. infusion, showing similar dynamics as P40D800 tracer. Postmortem in situ imaging and histology showed perineural accumulations of RBCs around the optic and olfactory nerves. Numerous RBCs cleared through the lymphatics of the cribriform plate, whilst histology showed no relevant fast RBC clearance through dorsal dural lymphatics or by tissue-resident macrophage-mediated phagocytosis.
INTERPRETATION
This study provides evidence for rapid RBC drainage through the cribriform plate lymphatic vessels, whilst neither fast RBC clearance through dorsal dural lymphatics nor through spinal CSF efflux or phagocytosis was observed. Similar dynamics of P40D800 and RBCs imply open pathways for clearance that do not impose a barrier for RBCs. This finding suggests further evaluation of the cribriform plate lymphatic function and potential pharmacological targeting in models of SAH.
FUNDING
Swiss National Science Foundation (310030_189226), SwissHeart (FF191155).
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Pre-clinic Human Medicine > Theodor Kocher Institute |
UniBE Contributor: |
Madarasz, Adrian Michael, Xin, Li, Proulx, Steven Thomas |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2352-3964 |
Publisher: |
Elsevier |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
26 Aug 2024 09:43 |
Last Modified: |
15 Sep 2024 00:18 |
Publisher DOI: |
10.1016/j.ebiom.2024.105295 |
PubMed ID: |
39178745 |
Uncontrolled Keywords: |
Cranial nerves Cribriform plate Lymphatic vessels Red blood cells Subarachnoid haemorrhage |
BORIS DOI: |
10.48350/199968 |
URI: |
https://boris.unibe.ch/id/eprint/199968 |
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