<oai_dc:dc xmlns:dc="http://purl.org/dc/elements/1.1/" xmlns:oai_dc="http://www.openarchives.org/OAI/2.0/oai_dc/" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xsi:schemaLocation="http://www.openarchives.org/OAI/2.0/oai_dc/ http://www.openarchives.org/OAI/2.0/oai_dc.xsd">
  <dc:creator>Piguet PF</dc:creator>
  <dc:creator>Kan CD</dc:creator>
  <dc:creator>Vesin C</dc:creator>
  <dc:date>2002</dc:date>
  <dc:description xmlns:ns0="xml" ns0:lang="en">Infection of susceptible mice with Plasmodium berghei Anka leads to a syndrome of severe or cerebral malaria. Tumor necrosis factor (TNF) contributes to this syndrome, apparently by acting on its receptor 2 (TNFR2) because TNFR1-/- are susceptible, whereas TNFR2-/- mice are resistant. In this work, we confirmed the essential role of the TNFR2 in cerebral malaria because 6 to 8 days after Plasmodium berghei Anka infection, hypothermia, coma, and death were observed in +/+ or TNFR1-/-, but never in TNFR2-/-, mice. TNF production, evaluated by the serum levels or the mRNA levels in the brain, spleen or lung, was similar in +/+, TNFR1-/-, or TNFR2-/- mice. Macrophage or parasitized red blood cell sequestration in brain or lung was similar in TNFR1-/- and TNFR2-/- mice. Accordingly, up-regulation of CD54 or CD40 in brain or lung was also similar in TNFR1-/- or TNFR2-/- mice. Platelet loss, manifested by thrombocytopenia and the presence of microparticles in plasma, was similar in TNFR1-/- or TNFR2-/- mice. Breakdown of the blood-brain barrier, detected by the diffusion of tracers, was attenuated in both TNFR1-/- and TNFR2-/-, compared with +/+, mice. Endothelial cells from brain capillaries, examined by transmission electron microscopy, were similar in infected TNFR1-/- or TNFR2-/- mice, whereas the basement membrane was enlarged in TNFR1-/- mice. Hypothermic mice were also hyperglycemic, and this was evident in +/+ and TNFR1-/-, but not in TNFR2-/-, mice. In addition, infected +/+ and TNFR1-/- mice became insulin resistant, while in contrast TNFR2-/- became extremely insulin sensitive. This study supports the possibility that coma and death are mediated not by cell sequestration or breakdown of vascular permeability, similar in TNFR1-/- or TNFR2-/- mice, but by metabolic disturbances selectively mediated by the TNFR2.</dc:description>
  <dc:format>application/pdf</dc:format>
  <dc:identifier>https://sonar.ch/global/documents/152615</dc:identifier>
  <dc:language>eng</dc:language>
  <dc:relation>info:eu-repo/semantics/altIdentifier/doi/10.1097/01.lab.0000028822.94883.8a</dc:relation>
  <dc:relation>info:eu-repo/semantics/altIdentifier/pmid/12218076</dc:relation>
  <dc:rights>info:eu-repo/semantics/openAccess</dc:rights>
  <dc:source>Laboratory investigation; a journal of technical methods and pathology. - 2002</dc:source>
  <dc:subject xmlns:ns1="xml" ns1:lang="en">Animals</dc:subject>
  <dc:subject xmlns:ns2="xml" ns2:lang="en">Antigens, CD</dc:subject>
  <dc:subject xmlns:ns3="xml" ns3:lang="en">Brain</dc:subject>
  <dc:subject xmlns:ns4="xml" ns4:lang="en">CD4 Antigens</dc:subject>
  <dc:subject xmlns:ns5="xml" ns5:lang="en">CD40 Antigens</dc:subject>
  <dc:subject xmlns:ns6="xml" ns6:lang="en">CD40 Ligand</dc:subject>
  <dc:subject xmlns:ns7="xml" ns7:lang="en">Capillary Permeability</dc:subject>
  <dc:subject xmlns:ns8="xml" ns8:lang="en">Coma</dc:subject>
  <dc:subject xmlns:ns9="xml" ns9:lang="en">Erythrocytes</dc:subject>
  <dc:subject xmlns:ns10="xml" ns10:lang="en">Insulin</dc:subject>
  <dc:subject xmlns:ns11="xml" ns11:lang="en">Macrophages</dc:subject>
  <dc:subject xmlns:ns12="xml" ns12:lang="en">Malaria, Cerebral</dc:subject>
  <dc:subject xmlns:ns13="xml" ns13:lang="en">Mice</dc:subject>
  <dc:subject xmlns:ns14="xml" ns14:lang="en">Mice, Inbred C57BL</dc:subject>
  <dc:subject xmlns:ns15="xml" ns15:lang="en">Mice, Inbred CBA</dc:subject>
  <dc:subject xmlns:ns16="xml" ns16:lang="en">RNA, Messenger</dc:subject>
  <dc:subject xmlns:ns17="xml" ns17:lang="en">Receptors, Tumor Necrosis Factor</dc:subject>
  <dc:subject xmlns:ns18="xml" ns18:lang="en">Receptors, Tumor Necrosis Factor, Type I</dc:subject>
  <dc:subject xmlns:ns19="xml" ns19:lang="en">Receptors, Tumor Necrosis Factor, Type II</dc:subject>
  <dc:subject xmlns:ns20="xml" ns20:lang="en">Thrombocytopenia</dc:subject>
  <dc:title xmlns:ns21="xml" ns21:lang="en">Role of the tumor necrosis factor receptor 2 (TNFR2) in cerebral malaria in mice.</dc:title>
  <dc:type>http://purl.org/coar/resource_type/c_6501</dc:type>
</oai_dc:dc>