title: Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria.
abstract: BACKGROUND
  Cerebral malaria (CM) remains a significant cause of morbidity and mortality in children in sub-Saharan Africa. CM mortality has been associated with increased brain volume, seen on neuroimaging studies.
  
  
  METHODS
  To examine the potential role of blood metabolites and inflammatory mediators in increased brain volume in Malawian children with CM, an association study was performed between plasma metabolites, cytokine levels and phospholipase A2 (PLA2) activity with brain volume.
  
  
  RESULTS
  The metabolomics analysis demonstrated arachidonic acid and other lysophospholipids to be positively associated with brain swelling. These lipids are products of the PLA2 enzyme and an association of plasma PLA2 enzymatic activity with brain swelling was confirmed. TNFα, which can upregulate PLA2 activity, was associated with brain volume. In addition, CCL2 and IL-8 were also associated with brain volume. Some of these cytokines can alter endothelial cell tight junction proteins and increase blood brain barrier permeability.
  
  
  CONCLUSIONS
  Taken together, paediatric CM brain volume was associated with products of the PLA2 pathway and inflammatory cytokines. Their role in causality is unknown. These molecules will need to undergo testing in vitro and in animal models to understand their role in processes of increased brain volume. These observations provide novel data on host physiology associated with paediatric CM brain swelling, and may both inform pathogenesis models and suggest adjunct therapies that could improve the morbidity and mortality associated with paediatric CM.
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. vasiliki.pappa@phd.einstein.yu.edu.
authors.forename: Vasiliki
authors.initials: V
authors.lastname: Pappa
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. seydel@msu.edu.|Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 48824, USA. seydel@msu.edu.
authors.forename: Karl
authors.initials: K
authors.lastname: Seydel
authors.affiliation: Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY, 10461, USA. sanchit.gupta@med.einstein.yu.edu.
authors.forename: Sanchit
authors.initials: S
authors.lastname: Gupta
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. catherine.manix@phd.einstein.yu.edu.
authors.forename: Catherine M
authors.initials: CM
authors.lastname: Feintuch
authors.affiliation: Department of Radiology, University of Rochester, Rochester, NY, 14642, USA. Michael_Potchen@URMC.Rochester.edu.|Lusaka Apex Medical University, Medical Radiation Sciences, Lusaka, Zambia. Michael_Potchen@URMC.Rochester.edu.
authors.forename: Michael J
authors.initials: MJ
authors.lastname: Potchen
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. s.kampo154@gmail.com.
authors.forename: Samuel
authors.initials: S
authors.lastname: Kampondeni
authors.affiliation: Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY, 10461, USA. adam.goldman-yassen@med.einstein.yu.edu.
authors.forename: Adam
authors.initials: A
authors.lastname: Goldman-Yassen
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. mike.veenstra@phd.einstein.yu.edu.
authors.forename: Mike
authors.initials: M
authors.lastname: Veenstra
authors.affiliation: Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. lillie.lopez@einstein.yu.edu.
authors.forename: Lillie
authors.initials: L
authors.lastname: Lopez
authors.affiliation: Department of Epidemiology and Population Health, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. ryung.kim@einstein.yu.edu.
authors.forename: Ryung S
authors.initials: RS
authors.lastname: Kim
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. joan.berman@einstein.yu.edu.|Department of Pathology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. joan.berman@einstein.yu.edu.
authors.forename: Joan W
authors.initials: JW
authors.lastname: Berman
authors.affiliation: Blantyre Malaria Project, University of Malawi College of Medicine, Blantyre, Malawi. ttmalawi@msu.edu.|Department of Osteopathic Medical Specialties, College of Osteopathic Medicine, Michigan State University, East Lansing, MI, 48824, USA. ttmalawi@msu.edu.
authors.forename: Terrie
authors.initials: T
authors.lastname: Taylor
authors.affiliation: Department of Microbiology and Immunology, Albert Einstein College of Medicine, Bronx, NY, 10461, USA. johanna.daily@einstein.yu.edu.|Department of Medicine (Infectious Diseases), Albert Einstein College of Medicine, Bronx, NY, 10461, USA. johanna.daily@einstein.yu.edu.
authors.forename: Johanna P
authors.initials: JP
authors.lastname: Daily
mesh_terms: D000818:Animals; D001921:Brain / Q000473:pathology*; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D016207:Cytokines / Q000097:blood*; D006801:Humans; D007223:Infant; D050356:Lipid Metabolism; D008055:Lipids / Q000097:blood*; D016779:Malaria, Cerebral / Q000473:pathology*; D008295:Malawi; D054467:Phospholipases A2 / Q000378:metabolism*
chemical_list: D016207:Cytokines; D008055:Lipids; D054467:Phospholipases A2