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Coagulation disorder in experimental cerebral malária

Grant number: 10/18570-0
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): April 01, 2011
Effective date (End): March 31, 2015
Field of knowledge:Biological Sciences - Parasitology - Protozoology of Parasites
Principal researcher:Fabio Trindade Maranhão Costa
Grantee:Ana Carolina Andrade Vitor Kayano
Home Institution: Instituto de Biologia (IB). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil

Abstract

Malaria endangers 2.4 billion people, especially those exposed to infection by Plasmodium falciparum, responsible for approximately 100 to 300 million cases and 1 million deaths annually. Cerebral malaria, a severe form of disease, is a multifactorial process which leads to local damages in brain tissue resulting from the blockage of blood flow and general brain damages triggered by imbalance of host immune response. In addition to endothelial activation, platelet counts, anticoagulant levels and the presence of actived thrombin and procoagulant microparticles suggest a dysregulation of the coagulation, it has been found hemorrhagic spots, microthrombi and leukocytes in the brains of patients who succumb MC. However, the phenomena responsible for the pathological features of MC are still poorly understood.Through of arterial thrombus formation induced photochemically, mice infected with Plasmodium berghei ANKA (PbA), experimental cerebral malaria model, showed time for occlusion faster than mice infected with Plasmodium berghei NK65 (PbNK, non-cerebral strain). However, the prothrombin time and activated partial thromboplastin time were not altered. Furthermore, assays with artesunate treatment revealed that the presence of the parasite is essential for thrombus formation, however, there is no a correlation between time to thrombus formation and parasite load. Platelets play an important role in formation of arterial thrombus, however their number decreased in animals with malaria does not influence thrombus formation time. However, the analysis of platelets volume indicates their increased activity in PbA-infected mice. Furthermore, in cerebral endothelium of these animals there was a high expression of ICAM-1 (intracellular adhesion molecule) and EPCR (endothelial protein C receptor) and a slight increase in expression of TF (tissue factor). These results demonstrate a disturbance in haemostasis in experimental cerebral malaria, as well as in human malaria, and this phenotype is dependent on the parasite strain, platelet activity, endothelial activation and TCD8+ lymphocytes.

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Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
KAYANO, Ana Carolina Andrade Vitor. Coagulation disturbance in experimental cerebral malaria. 2016. Doctoral Thesis - Universidade Estadual de Campinas (UNICAMP). Instituto de Biologia Campinas, SP.

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