The murine model of experimental cerebral malaria (ECM) induced by Plasmodium berghei ANKA was used to investigate the relationship among pro-inflammatory cytokines, alterations in renal function biomarkers, and the induction of the TRAIL apoptosis pathway during malaria-associated acute kidney injury (AKI). Renal function was evaluated through the measurement of plasma creatinine and blood urea nitrogen (BUN). The mRNA expression of several cytokines and NaPi-IIa was quantified. Kidney sections were examined and cytokine levels were assessed using cytometric bead array (CBA) assays. The presence of glomerular IgG deposits and apoptosis-related proteins were investigated using in situ immunofluorescence assays and quantitative real-time PCR, respectively. NaPi-IIa downregulation in the kidneys provided novel insights into the pathogenesis of hypophosphatemia during CM. Histopathological analysis revealed characteristic features of severe malaria-associated nephritis, including glomerular collapse and tubular alterations. Pro-inflammatory cytokines, such as TNF-α, IL-1β, and IL-6, were upregulated. The TRAIL apoptosis pathway was significantly activated, implicating its role in renal apoptosis. The observed alterations in renal biomarkers and the downregulation of NaPi-IIa shed light on potential mechanisms contributing to renal dysfunction in ECM. The intricate balance between pro- and anti-inflammatory cytokines, along with the activation of the TRAIL apoptosis pathway, highlights the complexity of malaria-associated AKI and provides new therapeutic targets.

Malaria remains a major global health challenge. While treatments targeting parasite replication exist, effective interventions for neurological manifestations are scarce, necessitating new strategies for cerebral malaria. In this study, we investigated the effect of a single-chain variable fragment (scFv) against glycosylphosphatidylinositol (GPI) as an intervention tool to mitigate the effects of Plasmodium in a preclinical model. We used C57BL/6J mice infected with Plasmodium berghei-ANKA (PbA) and treated them with anti-GPI scFv or phosphate-buffered saline (PBS) on days 0, 3, and 6 post-infection. Uninfected controls were treated on the same days with scFv or PBS. The animals were evaluated for morbidity and mortality, body weight, parasitemia, blood count, cytokines, and histopathology. Results show that anti-GPI scFv prevented lethality in 71.4% of infected animals and promoted recovery from weight loss. Furthermore, the intervention inhibited neurological and systemic signs, reduced parasitemia, and improved hematological and histopathological parameters in the brain, lungs, and kidneys. In conclusion, anti-GPI scFv exerts a significant systemic effect on experimental cerebral malaria (ECM) pathology, representing a promising tool for severe manifestations of the disease.