Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria
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. To examine the potential role of blood metabolites and inflammatory mediators in increased brain...
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| Veröffentlicht in: | Malaria journal 2015-12, Vol.14 (504), p.513-513, Article 513 |
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| creator | Pappa, Vasiliki Seydel, Karl Gupta, Sanchit Feintuch, Catherine M Potchen, Michael J Kampondeni, Samuel Goldman-Yassen, Adam Veenstra, Mike Lopez, Lillie Kim, Ryung S Berman, Joan W Taylor, Terrie Daily, Johanna P |
| description | 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.
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.
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.
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. |
| doi_str_mv | 10.1186/s12936-015-1036-1 |
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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.
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.
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.</description><identifier>ISSN: 1475-2875</identifier><identifier>EISSN: 1475-2875</identifier><identifier>DOI: 10.1186/s12936-015-1036-1</identifier><identifier>PMID: 26691993</identifier><language>eng</language><publisher>England: BioMed Central Ltd</publisher><subject>Animals ; Brain - pathology ; Care and treatment ; Causes of ; Child ; Child, Preschool ; Cohort Studies ; Complications and side effects ; Cytokines ; Cytokines - blood ; Health aspects ; Humans ; Infant ; Inflammation ; Lipid Metabolism ; Lipids - blood ; Malaria ; Malaria, Cerebral - pathology ; Malawi ; Pediatrics ; Phospholipases A2 - metabolism ; Risk factors</subject><ispartof>Malaria journal, 2015-12, Vol.14 (504), p.513-513, Article 513</ispartof><rights>COPYRIGHT 2015 BioMed Central Ltd.</rights><rights>Copyright BioMed Central 2015</rights><rights>Pappa et al. 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c4091-8f4219fae199917acb66606fb3cc913cae318bf02ebe556c2bd52e204e2f7c383</citedby><cites>FETCH-LOGICAL-c4091-8f4219fae199917acb66606fb3cc913cae318bf02ebe556c2bd52e204e2f7c383</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687364/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC4687364/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26691993$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Pappa, Vasiliki</creatorcontrib><creatorcontrib>Seydel, Karl</creatorcontrib><creatorcontrib>Gupta, Sanchit</creatorcontrib><creatorcontrib>Feintuch, Catherine M</creatorcontrib><creatorcontrib>Potchen, Michael J</creatorcontrib><creatorcontrib>Kampondeni, Samuel</creatorcontrib><creatorcontrib>Goldman-Yassen, Adam</creatorcontrib><creatorcontrib>Veenstra, Mike</creatorcontrib><creatorcontrib>Lopez, Lillie</creatorcontrib><creatorcontrib>Kim, Ryung S</creatorcontrib><creatorcontrib>Berman, Joan W</creatorcontrib><creatorcontrib>Taylor, Terrie</creatorcontrib><creatorcontrib>Daily, Johanna P</creatorcontrib><title>Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria</title><title>Malaria journal</title><addtitle>Malar J</addtitle><description>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.
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.
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.
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.</description><subject>Animals</subject><subject>Brain - pathology</subject><subject>Care and treatment</subject><subject>Causes of</subject><subject>Child</subject><subject>Child, Preschool</subject><subject>Cohort Studies</subject><subject>Complications and side effects</subject><subject>Cytokines</subject><subject>Cytokines - blood</subject><subject>Health aspects</subject><subject>Humans</subject><subject>Infant</subject><subject>Inflammation</subject><subject>Lipid Metabolism</subject><subject>Lipids - blood</subject><subject>Malaria</subject><subject>Malaria, Cerebral - pathology</subject><subject>Malawi</subject><subject>Pediatrics</subject><subject>Phospholipases A2 - metabolism</subject><subject>Risk factors</subject><issn>1475-2875</issn><issn>1475-2875</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><recordid>eNptUk1v1DAQjRCIlsIP4IIsceGSknES27kgrSq-pJW4wNmaOJPGJYmDnW21_6E_mlltKS1CluWR5703nvHLstdQnAMY9T6BbEqVF1DnUHAAT7JTqHSdS6Prpw_ik-xFSldFAdpo-Tw7kUo10DTlaXa79YvvxEQrtmH0KyURerEOJJYhJN6jXzCR2Eix4Drc4F7g3Ak_9yNOE64h7oXbr-Gnn5mKkQSmFJzHlTpx49dBtBH9LK7DuJuIeSxDHaejd8JRJE6PYsIRo8eX2bMex0Sv7s6z7Menj98vvuTbb5-_Xmy2uauKBnLTVxKaHolbaECja5VSherb0rkGSodUgmn7QlJLda2cbLtakiwqkr12pSnPsg9H3WXXTtQ5mld-hV2inzDubUBvH2dmP9jLcG0rZXSpKhZ4dycQw68dpdVOPjkaR5wp7JIFXUNllKkVQ9_-A70Kuzhze4zSDYsZ3fxFXeJIlqcbuK47iNpNVQN_lzaSUef_QfHqaPIuzNR7vn9EgCPBxZBSpP6-RyjswUL2aCHLFrIHC1lgzpuHw7ln_PFM-RvIH8Pc</recordid><startdate>20151221</startdate><enddate>20151221</enddate><creator>Pappa, Vasiliki</creator><creator>Seydel, Karl</creator><creator>Gupta, Sanchit</creator><creator>Feintuch, Catherine M</creator><creator>Potchen, Michael J</creator><creator>Kampondeni, Samuel</creator><creator>Goldman-Yassen, Adam</creator><creator>Veenstra, Mike</creator><creator>Lopez, Lillie</creator><creator>Kim, Ryung S</creator><creator>Berman, Joan W</creator><creator>Taylor, Terrie</creator><creator>Daily, Johanna P</creator><general>BioMed Central Ltd</general><general>BioMed Central</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7SS</scope><scope>7U9</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>F1W</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>H95</scope><scope>H97</scope><scope>K9.</scope><scope>L.G</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20151221</creationdate><title>Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria</title><author>Pappa, Vasiliki ; Seydel, Karl ; Gupta, Sanchit ; Feintuch, Catherine M ; Potchen, Michael J ; Kampondeni, Samuel ; Goldman-Yassen, Adam ; Veenstra, Mike ; Lopez, Lillie ; Kim, Ryung S ; Berman, Joan W ; Taylor, Terrie ; Daily, Johanna P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c4091-8f4219fae199917acb66606fb3cc913cae318bf02ebe556c2bd52e204e2f7c383</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>Animals</topic><topic>Brain - 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Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Malaria journal</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Pappa, Vasiliki</au><au>Seydel, Karl</au><au>Gupta, Sanchit</au><au>Feintuch, Catherine M</au><au>Potchen, Michael J</au><au>Kampondeni, Samuel</au><au>Goldman-Yassen, Adam</au><au>Veenstra, Mike</au><au>Lopez, Lillie</au><au>Kim, Ryung S</au><au>Berman, Joan W</au><au>Taylor, Terrie</au><au>Daily, Johanna P</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria</atitle><jtitle>Malaria journal</jtitle><addtitle>Malar J</addtitle><date>2015-12-21</date><risdate>2015</risdate><volume>14</volume><issue>504</issue><spage>513</spage><epage>513</epage><pages>513-513</pages><artnum>513</artnum><issn>1475-2875</issn><eissn>1475-2875</eissn><abstract>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.
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.
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.
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.</abstract><cop>England</cop><pub>BioMed Central Ltd</pub><pmid>26691993</pmid><doi>10.1186/s12936-015-1036-1</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
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| subjects | Animals Brain - pathology Care and treatment Causes of Child Child, Preschool Cohort Studies Complications and side effects Cytokines Cytokines - blood Health aspects Humans Infant Inflammation Lipid Metabolism Lipids - blood Malaria Malaria, Cerebral - pathology Malawi Pediatrics Phospholipases A2 - metabolism Risk factors |
| title | Lipid metabolites of the phospholipase A2 pathway and inflammatory cytokines are associated with brain volume in paediatric cerebral malaria |
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