Evaluation of hyperbaric oxygen (HBO) protective mechanisms on experimental cerebral malaria and on parasite's cytoadhesion

Abstract

Undoubtedly, malaria is the most important parasitic disease, infecting annually 300 - 500 million of individuals. Although the majority of cases remains uncomplicated, 1-3 million of those infections evolve to severe complications, leading to severe forms of the disease (severe malaria), such as; cerebral malaria (MC) and pregnancy associated malaria (PAM). MC is a multifactorial phenomenon and mediated by the adhesion of infected erythrocytes (IE) to several receptors expressed on the surface of microvasculature endothelial cells. Besides the parasite's cytoadhesion, MC patients display an immune response unbalance, leading to high levels of inflammatory cytokines and expression of host receptors involved in leukocyte adhesion, augmentation of lactate levels and intracranial pressure, and also a dysfunction on the blood-brain barrier (BBB) and coagulation cascade. Furthermore, in experimental cerebral malaria (ECM) nitric oxide (NO) plays a pivotal role on MC pathogenesis, and NO low biodisponibility leads to ECM associate symptoms and death. We have previously shown that hyperbaric oxygen (HBO) is able to delay, and also protect, against the symptoms in ECM, acting, in part, by reducing ECM inflammatory process. Importantly, it has been shown that HBO reduces ischemic and inflammatory process, by diminishing ICAM-1 expression levels Herein, we intend to expand the understanding on HBO protective effect against MC, taken in account not only the NO participation, but also the coagulation process on MC experimental model. Moreover, we plan to analyze the HBO effect on Plasmodium falciparum adhesion process to human and monkey endothelial cells under static and flow conditions; which takes in account the blood pressure. (AU)