TRPV1 Contributes to Cerebral Malaria Severity and Mortality by Regulating Brain Inflammation

Figure 7

Brain and vascular changes in cerebral malaria in TRPV1 WT and KO mice. (a) Several alterations occur in the brain tissue and vasculature during cerebral malaria. Wild-type (WT) red blood cells (RBC) infected with Plasmodium berghei ANKA reach the brain vasculature and trigger the accumulation of leukocytes in the vascular space. As a result of this close interaction between infected RBC, leukocytes, and the endothelium, oxidative stress products (H₂O₂, nitrosylated and carbonylated proteins) and cytokines (TNFα, IL-6, and IFNγ) are detected in the circulation and in the brain tissue; H₂O₂ levels are a lot higher in the brain tissue in comparison with the circulation. Plasma extravazation is increased in the brain and this is associated with reduced mRNA expression of the tight-junction endothelial markers claudin-5 and JAM-A. These alterations may culminate with neuronal death, thus, contributing to the increased morbidity and mortality observed in WT mice following infection with P. berghei ANKA. (b) Infected mice lacking TRPV1 (TRPV1KO) present increased levels of H₂O₂ and nitrosylated and carbonylated proteins than WT animals at both brain tissue and circulation. TRPV1KOs also exhibit lower concentrations of plasma and brain cytokines, especially TNFα and IL-6, and less plasma extravazation than WT mice, a response that is accompanied by higher expression of claudin-5 and JAM-A in their brain vasculature. The inflammatory response profile observed in TRPV1KO mice may reflect in less neuronal damage, as these animals are protected from P. berghei ANKA-induced death and symptoms.