Last Updated: 17/12/2025
The role of plasminogen activator inhibitor-1 during experimental cerebral malaria
Objectives
This study will evaluate the effect of an orally efficacious chemical inhibitor of plasminogen activator inhibitor 1 (PAI-1), tiplaxtinin, in the inhibition of experimental cerebral malaria (ECM) model induced by the rodent-infecting P. berghei ANKA parasites. It will evaluate the pathophysiology of tixplatinin treated ECM, including cognitive impairment, vascular disfunction and finally, death.
Cerebral malaria (CM) is the most severe neurological complication of falciparum malaria. CM kills about 500 thousand people every year. More than just killing, cerebral malaria leaves markers of its infection and 25% of those survivors have some neuronal sequel for long-term periods, even after parasite elimination. CM is caused by P. falciparum parasites, which can adhere to brain endothelial cells and disrupt the blood brain barrier. Moreover, CM leads to hemostatic disorder and activate the immune system resulting in neuroinflammation. The mechanisms of CM pathogenesis have not been fully elucidated, and there is no consensus on the main triggering factor. It is believed that three components are key to the development of this syndrome: parasite adhesion, endothelial dysfunction and inflammation. Clinically, CM is defined as a spread encephalophaty characterized by seizures and loss of consciousness. Several parameters are altered during CM, including levels of plasminogen activator inhibitor 1 (PAI-1) that were elevated in children from Zambia with CM. Taking that on consideration, we postulated that a PAI-1 inhibitor could prevent cerebral malaria. This project has the potential to identify a novel candidate target and therapy to treat this lethal syndrome..
Jan 2016
Related Resources
