Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA
Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have be...
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description | Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM. |
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Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.</description><identifier>ISSN: 0031-1820</identifier><identifier>EISSN: 1469-8161</identifier><identifier>DOI: 10.1017/S0031182016001475</identifier><identifier>PMID: 27574013</identifier><language>eng</language><publisher>Cambridge, UK: Cambridge University Press</publisher><subject>Animal models ; Animal Structures - parasitology ; Animal Structures - pathology ; Animals ; Disease Models, Animal ; Erythrocytes ; Histocytochemistry ; Malaria ; Malaria, Cerebral - parasitology ; Malaria, Cerebral - pathology ; Mice ; Microscopy ; Plasmodium berghei ; Plasmodium berghei - growth & development ; Plasmodium berghei - pathogenicity ; Plasmodium falciparum ; Vector-borne diseases</subject><ispartof>Parasitology, 2016-10, Vol.143 (12), p.1672-1680</ispartof><rights>Copyright © Cambridge University Press 2016</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c406t-22f08c1fd9d3aaf7a328db2b10b0ab32184862e9ad6b21c18d34d6d6826dcb843</citedby><cites>FETCH-LOGICAL-c406t-22f08c1fd9d3aaf7a328db2b10b0ab32184862e9ad6b21c18d34d6d6826dcb843</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.cambridge.org/core/product/identifier/S0031182016001475/type/journal_article$$EHTML$$P50$$Gcambridge$$H</linktohtml><link.rule.ids>164,314,780,784,27923,27924,55627</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27574013$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>DING, YAN</creatorcontrib><creatorcontrib>XU, WENYUE</creatorcontrib><creatorcontrib>ZHOU, TAOLI</creatorcontrib><creatorcontrib>LIU, TAIPING</creatorcontrib><creatorcontrib>ZHENG, HONG</creatorcontrib><creatorcontrib>FU, YONG</creatorcontrib><title>Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA</title><title>Parasitology</title><addtitle>Parasitology</addtitle><description>Malaria remains one of the most devastating diseases. Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.</description><subject>Animal models</subject><subject>Animal Structures - parasitology</subject><subject>Animal Structures - pathology</subject><subject>Animals</subject><subject>Disease Models, Animal</subject><subject>Erythrocytes</subject><subject>Histocytochemistry</subject><subject>Malaria</subject><subject>Malaria, Cerebral - parasitology</subject><subject>Malaria, Cerebral - pathology</subject><subject>Mice</subject><subject>Microscopy</subject><subject>Plasmodium berghei</subject><subject>Plasmodium berghei - growth & development</subject><subject>Plasmodium berghei - pathogenicity</subject><subject>Plasmodium falciparum</subject><subject>Vector-borne diseases</subject><issn>0031-1820</issn><issn>1469-8161</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNqNkU1v1DAQhi0EotuFH8AFWeLCJTBju45zXFUFqn6ABJwjf0x2XcVJsRMh_j3ZdkGIConTaGae9x2NXsZeILxBwPrtZwCJaASgBkBVnzxiK1S6qQxqfMxW-3W13x-x41JuAEBLLZ6yI1Gf1ApQrlg8K5N1fSy7RMPEx45bnuYcB-JpDNTvJ54yuWx7nmxvc7Q8DvxiHq7isOUpelr6jvxEgX-P045_6m1ZtHFO3FHe7ijyzfXF5hl70tm-0PNDXbOv786-nH6oLj--Pz_dXFZegZ4qITowHrvQBGltV1spTHDCITiwTgo0ymhBjQ3aCfRoglRBB22EDt4ZJdfs9b3vbR6_zVSmNsXiqe_tQONcWjTaSNnUSv8Hik0DSiyCNXv1F3ozznlYHrmjhFQgxELhPeXzWEqmrr3NMdn8o0Vo95G1DyJbNC8PzrNLFH4rfmW0APJgapPLMWzpj9v_tP0JXVieiw</recordid><startdate>201610</startdate><enddate>201610</enddate><creator>DING, YAN</creator><creator>XU, WENYUE</creator><creator>ZHOU, TAOLI</creator><creator>LIU, TAIPING</creator><creator>ZHENG, HONG</creator><creator>FU, YONG</creator><general>Cambridge University Press</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>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TM</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ATCPS</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>P64</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>RC3</scope><scope>7X8</scope></search><sort><creationdate>201610</creationdate><title>Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA</title><author>DING, YAN ; 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Cerebral malaria (CM) is a severe complication of Plasmodium falciparum infection resulting in high mortality and morbidity worldwide. Analysis of precise mechanisms of CM in humans is difficult for ethical reasons and animal models of CM have been employed to study malaria pathogenesis. Here, we describe a new experimental cerebral malaria (ECM) model with Plasmodium berghei ANKA infection in KunMing (KM) mice. KM mice developed ECM after blood-stage or sporozoites infection, and the development of ECM in KM mice has a dose-dependent relationship with sporozoites inoculums. Histopathological findings revealed important features associated with ECM, including accumulation of mononuclear cells and red blood cells in brain microvascular, and brain parenchymal haemorrhages. Blood–brain barrier (BBB) examination showed that BBB disruption was present in infected KM mice when displaying clinical signs of CM. In vivo bioluminescent imaging experiment indicated that parasitized red blood cells accumulated in most vital organs including heart, lung, spleen, kidney, liver and brain. The levels of inflammatory cytokines interferon-gamma, tumour necrosis factor-alpha, interleukin (IL)-17, IL-12, IL-6 and IL-10 were all remarkably increased in KM mice infected with P. berghei ANKA. This study indicates that P. berghei ANKA infection in KM mice can be used as ECM model to extend further research on genetic, pharmacological and vaccine studies of CM.</abstract><cop>Cambridge, UK</cop><pub>Cambridge University Press</pub><pmid>27574013</pmid><doi>10.1017/S0031182016001475</doi><tpages>9</tpages></addata></record> |
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subjects | Animal models Animal Structures - parasitology Animal Structures - pathology Animals Disease Models, Animal Erythrocytes Histocytochemistry Malaria Malaria, Cerebral - parasitology Malaria, Cerebral - pathology Mice Microscopy Plasmodium berghei Plasmodium berghei - growth & development Plasmodium berghei - pathogenicity Plasmodium falciparum Vector-borne diseases |
title | Establishment of a murine model of cerebral malaria in KunMing mice infected with Plasmodium berghei ANKA |
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