Lymphatic network drainage resolves cerebral edema and facilitates recovery from experimental cerebral malaria.

CP: Neuroscience Plasmodium brain cerebral edema cerebral malaria lymphatics

Journal

Cell reports
ISSN: 2211-1247
Titre abrégé: Cell Rep
Pays: United States
ID NLM: 101573691

Informations de publication

Date de publication:
09 May 2024
Historique:
received: 22 11 2022
revised: 29 11 2023
accepted: 25 04 2024
medline: 10 5 2024
pubmed: 10 5 2024
entrez: 10 5 2024
Statut: aheadofprint

Résumé

While brain swelling, associated with fluid accumulation, is a known feature of pediatric cerebral malaria (CM), how fluid and macromolecules are drained from the brain during recovery from CM is unknown. Using the experimental CM (ECM) model, we show that fluid accumulation in the brain during CM is driven by vasogenic edema and not by perivascular cerebrospinal fluid (CSF) influx. We identify that fluid and molecules are removed from the brain extremely quickly in mice with ECM to the deep cervical lymph nodes (dcLNs), predominantly through basal routes and across the cribriform plate and the nasal lymphatics. In agreement, we demonstrate that ligation of the afferent lymphatic vessels draining to the dcLNs significantly impairs fluid drainage from the brain and lowers anti-malarial drug recovery from the ECM syndrome. Collectively, our results provide insight into the pathways that coordinate recovery from CM.

Identifiants

pubmed: 38728141
pii: S2211-1247(24)00545-X
doi: 10.1016/j.celrep.2024.114217
pii:
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

114217

Informations de copyright

Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.

Déclaration de conflit d'intérêts

Declaration of interests The authors declare no competing interests.

Auteurs

Michael J Haley (MJ)

Division of Immunology, Immunity to Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.

Ruben Barroso (R)

Division of Immunology, Immunity to Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK.

Dhifaf A Jasim (DA)

Nanomedicine Lab, National Graphene Institute and Faculty of Biology, Medicine & Health, The University of Manchester, AV Hill Building, Manchester M13 9PT, UK; Medicines Discovery Catapult (MDC), Alderley Park, Macclesfield SK10 4TG, UK.

Megan Haigh (M)

Division of Immunology, Immunity to Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK.

Jack Green (J)

Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK; Division of Neuroscience, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK.

Ben Dickie (B)

Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; Division of Informatics, Imaging & Data Sciences, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK.

Alister G Craig (AG)

Department of Tropical Disease Biology, Liverpool School of Tropical Medicine, Liverpool L3 5QA, UK.

David Brough (D)

Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK; Division of Neuroscience, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK.

Kevin N Couper (KN)

Division of Immunology, Immunity to Infection & Respiratory Medicine, Faculty of Biology, Medicine & Health, The University of Manchester, Manchester M13 9PT, UK; Geoffrey Jefferson Brain Research Centre, The Manchester Academic Health Science Centre, Northern Care Alliance NHS Group, University of Manchester, Manchester, UK; The Lydia Becker Institute of Immunology and Inflammation, University of Manchester, Manchester, UK. Electronic address: kevin.couper@manchester.ac.uk.

Classifications MeSH