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

• Published in: Cell reports (Cambridge) Vol. 43; no. 5; p. 114217
• Main Authors: Haley, Michael J., Barroso, Ruben, Jasim, Dhifaf A., Haigh, Megan, Green, Jack, Dickie, Ben, Craig, Alister G., Brough, David, Couper, Kevin N.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 28.05.2024; Elsevier
• Subjects: Animals; brain; Brain - metabolism; Brain - parasitology; Brain - pathology; Brain Edema; cerebral edema; cerebral malaria; CP: Neuroscience; Disease Models, Animal; Female; Lymph Nodes - pathology; Lymphatic Vessels - metabolism; lymphatics; Malaria, Cerebral - pathology; Male; Mice; Mice, Inbred C57BL; Plasmodium; Plasmodium berghei; Plasmodium; cerebral malaria; brain; cerebral edema; CP: Neuroscience; lymphatics
• ISSN: 2211-1247; 2211-1247
• DOI: 10.1016/j.celrep.2024.114217

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. [Display omitted] •Vasogenic edema is a pathological feature of experimental cerebral malaria (ECM)•Basal meningeal and nasal lymphatic networks clear edematous fluid during ECM•Ligation of deep cervical lymph nodes inhibits edematous fluid removal during ECM Haley et al. show that recovery from experimental cerebral malaria (ECM) is dependent on the rapid drainage of fluid from the skull through lymphatic vessels within the base of the brain and the nasal regions, connecting to the deep cervical lymph nodes.